PTK2 (PTK2 protein tyrosine kinase 2)

2011-03-01   Joerg Schwock , Neesha Dhani 





Cloning of the FAK cDNA and initial characterization of the kinase was accomplished independently by three groups in 1992 (Schaller et al., 1992; Hanks et al., 1992; Guan and Shalloway 1992). The cDNA of the human FAK homologue was first cloned by André and Becker-André (1993). The position of the human PTK2 gene encoding FAK on chromosome 8 was first predicted by Fiedorek and Kay (1995).


Initial expression studies using reverse transcriptase PCR detected FAK mRNA in a series of lymphoid cell lines as well as HeLa and SK-N-SH neuroblastoma cells indicating ubiquitous expression. Only a lymphocyte adhesion deficient cell line tested negative for the FAK transcript (André and Becker-André 1993). Transcripts of different sizes were detected in different human tissues in the same study with differential expression patterns for these transcripts noted in brain, lung, heart, liver and placenta.
Several transcript variants encoding different FAK isoforms have been found for the PTK2 gene. The full-length nature of the following three has been determined.

- Variant 1 differs in the 5 UTR and coding sequence compared to variant 2. The resulting isoform (a) is shorter at the N-terminus compared to isoform (b).
4414 bp - 33 exons - 1065 aa.
Ave. residue weight: 113.521.
Charge: 3.5.
Isoelectric point: 6.7311.
Molecular weight: 120899.54.
Number of residues: 1065.

- Variant 2 encodes the longest isoform (b).
4286 bp - 31 exons - 1073 aa.
Ave. residue weight: 113.366.
Charge: 2.0.
Isoelectric point: 6.6317.
Molecular weight: 121641.45.
Number of residues: 1073.

- Variant 3 differs in the 5 UTR and coding sequence, and contains two additional in-frame segments near the 3 end of the coding sequence, compared to variant 2. The resulting isoform (c) is shorter at the N-terminus and contains two additional segments in the C-terminus compared to isoform b.



Focal adhesion kinase (FAK) is a cytoplasmic non-receptor protein tyrosine kinase which was isolated for the first time by co-immunoprecipitation of tyrosine-phosphorylated proteins from cells transformed with Rous sarcoma virus v-Src (Kanner et al., 1990).


FAK is a ubiquitously expressed protein composed of a N-terminal FERM domain (protein 4.1, ezrin, radixin, moesin), a kinase domain, three intervening proline-rich regions (PRR) and a C-terminal focal adhesion targeting (FAT) domain (Figure 1).
Atlas Image
Figure 1: Schematic of focal adhesion kinase domain structure with phosphorylation sites.




Cytoplasmic and nuclear.
Atlas Image
Figure 2: Immunohistochemical staining of FAK in invasive cancer of the uterine cervix. (Note the accentuation of the FAK staining at the margin of the tumor nests. Size bar, 1 mm). Method and antibody: Schwock et al., 2009.


FAK is characterized by a functional duality, serving as a kinase as well as a molecular scaffold. These two functions may be required independently or in concert depending on the context in which FAK-mediated signaling occurs (Sieg et al., 1999; Sieg et al., 2000). FAK regulates the dynamic of focal adhesion complexes which are sites of attachment between cells and extracellular matrix. Cyclic assembly and disassembly of these complexes at the leading and trailing edge of the cell is required for the migration of mesenchymal cells and those that adopt mesenchymal-like characteristics as a consequence of developmental processes or during disease states. The latter mainly encompasses forms of tissue repair (i.e. wound healing and fibrosis) as well as neoplasia (i.e. tumor invasion and metastasis). As an example, Figure 2 shows immunohistochemical staining for FAK in metastatic cancer of the uterine cervix. FAK has been implicated with the establishment of a front-back polarity (Tilghman et al., 2005), lamellipodial persistence at the leading edge (Owen et al., 2007) and release of adhesions at the trailing edge (Iwanicki et al., 2008).
Integrin engagement with the extracellular matrix results in integrin clustering and a sequence of inter- and intramolecular events that permit the autophosphorylation of FAK at Tyr397 (Dunty et al., 2004). Subsequent recruitment of Src-family kinases through SH2-domain binding is followed by a mutual activation of both kinases. In the case of FAK this further activation is accomplished by phosphorylation of other tyrosine residues, specifically Tyr407, 576, 577, 861 and 925. Phosphorylation of Tyr576 and 577 increases FAK kinase activity whereas the remaining tyrosine residues serve as docking sites for SH2-containing factors such as Grb2 which links FAK into the MAPK pathway. Tyr397 also constitutes a docking site for the p85 subunit of PI3K (Chen and Guan, 1994) and phospholipase C gamma (Zhang et al., 1999). The PRRs are sites of interaction with SH3-containing factors which transmit signals downstream of the kinase and regulate the activity of Rho-family GTPases in charge of cell motility through the formation of stress fibres (RhoA), lamellipodia (Rac) and filopodia (Cdc42). Crk-associated substrate (p130Cas), initially identified in a two-hybrid screen, is one of the main downstream factors that bind to the PRRs of FAK (Polte and Hanks, 1995). Signaling via p130Cas towards Crk, DOCK180 and Rac has been linked to membrane ruffling, lamellipodia formation and cell motility (Harte et al., 1996; Cho and Klemke, 2002). A second essential downstream target of FAK is paxillin (Bellis et al., 1995), an adaptor protein lacking intrinsic kinase activity which can be phosphorylated at two sites, Tyr31 and Tyr118, and binds FAK within the C-terminal focal adhesion targeting (FAT) region (Hayashi et al., 2002). Mutations in FAK that disrupt binding to paxillin affect the localization of the kinase to focal contacts. Paxillin may also be involved in regulation of MAPK downstream signaling due to an overlapping binding site with Grb2 which binds to Tyr925 within the FAT region (Liu et al., 2002).
More recent studies link FAK to the regulation of cell-cell contacts, microtubule stability and control of gene transcription. Conflicting results have been reported from different experimental systems implicating FAK either with the dissolution (Avizienyte et al., 2002; Cicchini et al., 2008) or the promotion (Yano et al., 2004; Playford et al., 2008) of cell-cell contacts which suggests a dependency of this feature on the specific cellular context. Ezratty et al. (2005) reported on the role of FAK, Grb2 and dynamin in microtubule-induced focal adhesion disassembly. Earlier studies demonstrated an integrin-mediated activation of FAK at the leading edge of migrating cells as requirement for microtubule stabilization mediated by Rho and mDia (Palazzo et al., 2004). This mechanism also involves localization of a lipid raft marker, ganglioside GM1, to the leading edge. Xie et al. (2003) showed that Cdk5-mediated serine-phosphorylation of FAK was linked to the localization of the kinase at microtubule fork structures which contribute to nuclear repositioning in migrating neuronal cells. Recently, serine-phosphorylated FAK was shown to co-localize with centrosomes in mitotic endothelial cells. In this study by Park et al. (2009), FAK was also found associated with cytoplasmic dynein, and deletion of FAK resulted in mitotic defects. In 2005, Golubovskaya et al. reported results indicating a physical interaction between the N-terminal fragment of FAK and the N-terminal transactivation domain of p53. This interaction led to suppression of p53-mediated apoptosis and inhibition of the transcriptional activity of p53. Lim et al. (2008) subsequently provided data demonstrating a scaffolding role of nuclear FAK for MDM2-mediated p53 degradation mediated by the different lobes of the FERM domain. Also, basic sequences in the F2 lobe of the FERM domain were implicated in the nuclear localization of FAK (Lim et al., 2008), but alternative mechanisms independent from this putative nuclear localization signal are thought to exist (Schaller, 2010). Another nuclear function was recently uncovered by Luo et al. (2009) who described a role of FAK in chromatin remodelling via its interaction with MBD2 leading to increased myogenin expression and muscle-terminal differentiation. Liu et al. (2004), Li et al. (2004) and Ren et al. (2004) reported an involvement of FAK in netrin-1 signaling downstream of the netrin receptor DCC with consequences for axonal outgrowth and guidance in the developing brain.
- Mouse Models
Several mouse models have been generated to elucidate the functions of FAK both during normal development and neoplasia. A role of FAK in embryonal development was first observed in fak-/- mice which displayed defects in mesoderm development and anterior-posterior axis formation with embryonic lethality around day E8.5 (Ilic et al., 1995).
A conditional knockout model using a Cre-loxP system with Cre recombinase under the control of the nkx2-5 promoter was generated by Hakim et al. (2007). The major abnormality reported from this study was a profound disturbance of the development of the cardiac outflow tract. Knockout mice from this study died shortly after birth and displayed a range of cardiac defects which resemble the human congenital heart defects Tetralogy of Fallot and persistent truncus arteriosus. Peng et al. (2006) and DiMichele et al. (2006) reported results obtained with conditional knockout mice which carried Cre-recombinase under the control of the myosin light chain 2v promoter. Peng et al. (2006) found that knockout mice developed eccentric cardiac hypertrophy upon stimulation with angiotensin II or pressure overload. In contrast, the results by DiMichele et al. (2006) suggest that FAK functions to promote cardiac hypertrophy. In a later study by Peng at al. (2008) with myosin light chain-2a Cre mice they observed cardiac developmental abnormalities with thin ventricular walls and ventricular septal defects in the knockout mice, the majority of which died in the embryonic stage. Endothelial cell-specific knockout of FAK, again using a Cre-loxP approach, has been reported by Shen et al. (2005) and Braren et al. (2006). The observed phenotypes in knockout mice from both studies strongly suggest a role of FAK in vascular morphogenesis, particularly vascular remodelling and sprouting angiogenesis. The roles of FAK in the cardiovascular system were reviewed by Vadali et al. (2007).
A series of mouse models suggest an essential role of FAK during the development of the central nervous system. Beggs et al. (2003) created dorsal forebrain-specific conditional knockout mice using the Cre/loxP approach and observed an essential function of FAK for the formation of a normal basal lamina at the interface between radial glial end-feet and meningeal fibroblasts. They noted that the cortical changes seen in their study resembled lissencephaly phenotypes seen in some forms of human congenital muscular dystrophy.
Van Miltenburg et al. (2009) investigated the role of FAK in normal mammary gland using a conditional FAK-knockout mammary epithelial cell transplantation model based on FAK(lox/lox)/Rosa26Cre-ERT2 donor mice with loss of FAK in all mammary cells. They observed an abnormal mammary duct development with a disruption of myoepithelial and luminal epithelial cell layer and aberrant ductal morphogenesis during pregnancy.
Comprehensive reviews focused on the cellular functions of FAK have been published by Mitra et al. (2005) and Schaller (2010). Figure 3 schematically summarizes some of the diverse cellular functions of FAK.
- Regulation
The level of FAK expression is negatively and positively regulated by several transcription factors including p53, NF-kB and N-Myc (Golubovskaya et al., 2004; Beierle et al., 2007). Aside from the tyrosine residues implicated with FAK activation, at least four different serine phosphorylation sites (Ser722, 840, 843 and 910) have been recognized within FAK. Although the function of these serine sites has been examined less comprehensively, their phosphorylation has generally been associated with FAK inactivation, such as during mitosis (Ma et al., 2001), in suspension and under conditions that disturb the integrity of the actin cytoskeleton (Jacamo et al., 2007). FAK signaling is subject to additional levels of regulation which involve proteolytic cleavage (Dourdin et al., 2001), sumoylation (Kadaré et al., 2003), inhibition by FAK family interacting protein of 200 kDa (FIP200) (Abbi et al., 2002), dephosphorylation by protein-tyrosine phosphatases (Zeng et al., 2003), and generation of alternatively spliced isoforms such as FAK-related non-kinase (FRNK) (Schaller et al., 1993).
- Other protein family members: Pyk2.
Atlas Image
Figure 3: Schematic of the Cellular Functions of FAK.


Homo sapiens PTK2% Identity forProteinDNA
vs. Pan troglodytes PTK299.899.7
vs. Canis lupus familiaris PTK297.091.7
vs. Mus musculus Ptk297.290.7
vs. Rattus norvegicus Ptk297.090.8
vs. Gallus gallus PTK294.9 83.9
vs. Danio rerio ptk2.183.274.2
vs. Drosophila melanogaster Fak56D42.948.9
vs. Caenorhabditis elegans kin-3236.547.8
(Source :

Implicated in

Entity name
Increased expression of FAK was first noticed in high-grade and metastatic sarcomas (Weiner et al., 1994) and later in pre-invasive as well as invasive epithelial neoplasms (Owens et al., 1995). In general, lower levels of FAK expression are found in normal tissues whereas the higher levels are present in metastatic cancer suggesting an involvement of the kinase in oncogenesis. In neoplastic conditions the kinase has been credited with a range of functions including tumor cell motility (Sieg et al., 1999), matrix degradation leading to distant spread (Hauck et al., 2002), suppression of apoptosis (Sonoda et al., 2000), anoikis (Frisch et al., 1996) and senescence (Pylayeva et al., 2009) as well as positive effects on angiogenesis (Mitra et al., 2006), vasculogenic mimicry (Hess et al., 2005) and hypoxia response (Skuli et al., 2009). Results from a Cre/loxP-mediated FAK-knockout model specific to mouse mammary epithelial cells revealed a reduced pool of cancer stem/progenitor cells after FAK deletion which suggests that the kinase may not only support tumor cell dissemination to distant sites, but also the colonization of the target organ and establishment of a new tumor mass (Luo et al., 2009). Other transgenic mouse models focused on the role of FAK in neoplasia have been reported by McLean et al. (2004) for skin and by Lahlou et al. (2007), Provenzano et al. (2008) and Pylayeva et al. (2009) for mammary tumor formation and progression.
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Nervous system
The role of FAK in glioma tumor progression and in the regulation of the permeability of tumor-associated vasculature has been described, as well as the therapeutic efficacy of FAK inhibition by both pharmacologic compounds and liposomal-mediated RNA interference (Shi et al., 2007; Lipinski et al., 2008; Lee et al., 2010; Wang et al., 2011). Immunohistochemical analysis of 96 patient biopsies demonstrated higher levels of total and phosphorylated FAK in high grade tumors which correlated with inferior patient survival (Ding et al., 2010).
Beierle et al. (2007) reported on the relevance of FAK as cellular survival factor in N-myc-amplified neuroblastoma and identified N-myc binding sites in the FAK promoter. Recently, the same group also provided data indicating greater in vivo-therapeutic efficacy of pharmacologic FAK inhibition in N-myc-positive model systems (Beierle et al., 2010a; Beierle et al., 2010b). Efficacy of a novel small molecule dual IGF1R/FAK tyrosine kinase inhibitor (TAE226) leading to decreased FAK phosphorylation and cellular viability, cell cycle arrest and apoptosis has been described in human neuroblastoma cell lines (Beierle et al., 2008b). FAK expression was demonstrated in 51 of 70 clinical neuroblastoma samples by immunohistochemistry. FAK protein levels correlated with mRNA transcript levels and with advanced disease stage in this study (Beierle et al., 2008a).
Entity name
Head and neck squamous cell carcinoma
FAK has been linked to invasion in squamous cell carcinoma of the head and neck through promotion of cell motility and MMP-2 production (Canel et al., 2008). FAK gene and protein expression were previously evaluated in 211 clinical samples which included tissue from cases of dysplasia and benign hyperplasia (Canel et al., 2006). In this study, 62% of the primary cancers had high FAK protein expression, and the levels were consistent with those seen in corresponding lymph node metastases. A recent preclinial study has implicated FAK phosphorylation levels with radioresistance (Hehlgans et al., 2009).
Entity name
Thyroid carcinoma
Immunohistochemical staining of 108 patient samples for FAK protein discriminated malignant from benign thyroid lesions. FAK levels correlated with tumor size and capsular/lymphatic invasion (Michailidi et al., 2010). Previously, Kim et al. (2004) reported FAK expression in follicular, papillary, medullary and anaplastic thyroid carcinomas. FAK was not expressed in normal thyroid tissue and nodular hyperplasia, but in some of the follicular adenomas included in their study.
Entity name
Breast cancer
Lahlou et al. (2007) reported a block in tumor progression in a transgenic mouse model of breast cancer with disrupted FAK function based on Cre/loxP recombination. An earlier immunohistochemical study on clinical breast tissue showed increased FAK expression in ductal carcinoma in situ compared to atypical ductal hyperplasia and invasive ductal carcinoma (Lightfoot et al., 2004). The authors of this study concluded that FAK overexpression precedes tumor cell invasion and metastasis. Subsequently, a study by Lark et al. (2005) in 629 breast cancer samples correlated high FAK protein expression with poor prognostic indicators such as high mitotic index and nuclear grade, negative hormone receptor status, and Her2/neu over-expression. Schmitz et al. (2005) provided further evidence to support Her2/neu downstream signaling through FAK/Src-mediated pathways. Recently, a positive correlation between FAK over-expression and p53 mutation status has been reported (Golubovskaya et al., 2008; Golubovskaya et al., 2009). Yom et al. (2010) evaluated 435 cases of invasive ductal cancer for FAK gene copy number by fluorescence in situ hybridization (FISH) and FAK protein expression by immunohistochemistry, both of which correlated with features of aggressive tumor biology. Concordance between FISH and immunohistochemistry results was observed in 74.9%. An increased gene copy number by FISH correlated significantly with inferior patient outcome in this study.
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Lung cancer
Array comparative genomic hybridization studies on clinical samples of small cell lung cancer demonstrated regions of copy number alternations (gains and losses) enriched for genes involved in focal adhesion signaling. This included gains of FAK copy number which was confirmed in a smaller subset of the original 46 cases by FISH and quantitative RT-PCR. FAK was also highly expressed in tumor tissue (90% of 52 samples) in comparison with normal lung samples (Ocak et al., 2010). Wang et al. (2009) reported results of their study focused on FAK expression in bronchio-alveolar carcinoma (BAC) and lung adenocarcinomas. They found that in lung adenocarcinoma overall survival was better for patients with FAK-negative compared with FAK-positive tumors. A study by Hiratsuka et al. (2011) implicated endothelial FAK and E-selectin with the formation of lung metastasis from distant primary tumors due to the formation of discrete foci of vascular hyper-permeability important for the initial homing of metastatic cancer cells to the lungs.
Entity name
Gastro-intestinal tract cancer
Giaginis et al. (2009) reported results of an immunohistochemical study performed on the two major subtypes of gastric adenocarcinoma, including 30 cases of intestinal- and 36 cases of diffuse-type. Although FAK staining in diffuse-type gastric cancer correlated with larger tumor size and advanced disease stage, it also correlated with longer overall survival. For intestinal type cancer, however, an association with increased proliferative capacity and a non-significant trend to inferior survival was reported. A retrospective study including 444 surgical samples demonstrated a positive correlation between FAK gene amplification and protein expression levels with tumor size, lymphovascular invasion and nodal/distant metastases (Park et al., 2010). Focal adhesion kinase protein expression and gene amplification were positively correlated with each other in this study, and each of them was found to be an independent poor prognostic factor.
FAK has been implicated in invasion and metastasis as well as chemoresistance in pancreatic cancer (Duxbury et al., 2003; Duxbury et al., 2004). FAK overexpression by immunohistochemistry, demonstrated in 24 of 50 (48%) patient samples, correlated with tumor size, but no other features including grade, lymph node involvement or metastasis in a study by Furuyama et al. (2006). Another study included an examination of both FAK and Src protein levels. FAK expression correlated significantly with tumor stage while Src expression correlated with both tumor stage and patient survival, and was identified as an independent prognostic factor by multivariate analysis (Chatzizacharias et al., 2010).
Hayashi et al. (2010) demonstrated high levels of cytoplasmic FAK expression in normal biliary epithelium and observed a gradual loss of staining from dysplasia to extra-hepatic bile duct carcinoma. In this study, positive FAK staining was associated with a significantly better survival. Increased levels of FAK mRNA and protein have also been observed in a study of 60 patients with hepatocellular cancers. Increased mRNA levels correlated with tumor size, serum AFP and inferior disease-free and overall survival (Fujii et al., 2004).
RNA interference studies in colorectal cancer cell line xenografts demonstrated that FAK inhibition resulted in inhibition of cell proliferation and angiogenesis, induction of apoptosis and tumor growth suppression (Lei et al., 2010). Elevated levels of FAK mRNA and protein were noted in a small cohort of 34 matched primary colon cancers and liver metastases (Lark et al., 2003). More recently a larger series of colorectal cancers with matched liver metastases was used to evaluate the correlation of FAK staining with clinical outcome. In this study, FAK staining was equivalent in primary and metastatic lesions, and elevated levels of FAK and Src were associated with a reduced time to recurrence (de Heer et al., 2008).
Entity name
Female genital tract cancer
FAK has been implicated in the invasive and metastatic phenotype of ovarian cancer through multiple pathways (Hu et al., 2008; Yagi et al., 2008). In one report, MUC4-induced epithelial-mesenchymal transition was partially mediated by FAK, and pharmacologic FAK inhibition successfully abrogated MUC4-induced cell motility (Ponnusamy et al., 2010). In another study, cooperative signaling of c-met and alpha5beta1 integrin through FAK/Src was associated with promotion of invasion and metastases (Mitra et al., 2010). FAK activation also appears to be relevant to the development of resistance to standard cytotoxics (Halder et al., 2005; Villedieu et al., 2006) and preclinical studies have demonstrated therapeutic efficacy of various methods of FAK inhibition including pharmacologic inhibition and RNA interference (Halder et al., 2006; Halder et al., 2007; Yang et al., 2007). Sood et al. (2010) recently described protection from anoikis by catecholamine signaling mediated by FAK. They concluded that these results support a role for FAK signaling in the stress-mediated promotion of aggressive tumor biology. They also demonstrated increased levels of FAK and phosphorylated FAK in greater than 50% of the examined tumors, both of which correlated with inferior patient survival. Two earlier studies documented up-regulation of FAK protein and phosphorylated FAK in invasive ovarian cancers in comparison with normal epithelium (Sood et al., 2004; Grisaru-Granovsky et al., 2005). Sood et al. (2004) also noted associations between FAK immunohistochemical staining and more advanced tumor stage, tumor grade, metastasis and inferior overall survival.
Immunohistochemical analysis of 134 cases of endometrial cancer demonstrated moderate to strong staining in the majority (89%) of cases. Weak FAK staining was noted in the remaining 11% and associated with a trend to improved survival. Increased FAK staining, however, correlated with measures of poor outcome including tumor grade, lymphovascular invasion and lymph node metastases (Gabriel et al., 2009). A different study demonstrated high levels of FAK expression in endometrial cancers of different histologies (endometrioid, serous and clear cell) as well as in regions of endometrial hyperplasia. The authors concluded that their data implicate FAK in endometrial carcinogenesis (Livasy et al., 2004).
An analysis of 166 surgical samples demonstrated cytoplasmic and membranous FAK staining in regions of cervical dysplasia and frankly invasive cancer of the uterine cervix with absent staining in adjacent normal cervical epithelium (Gabriel et al., 2006). One third of the patients, with tumors exhibiting weak FAK staining, had an inferior survival compared to those with moderate/strong FAK staining, and weak FAK staining correlated with lymph node positivity in this study. Oktay et al. (2003) demonstrated positive FAK staining in premalignant lesions. Similarly, Schwock et al. (2009) demonstrated an increase in FAK expression and concurrent decrease of E-cadherin in metastatic cervical cancer and carcinoma in-situ compared to normal cervical epithelium. An association between E-cadherin loss and FAK was also noted in an earlier study that included 26 carcinomas and 5 carcinoma in situ cases (Moon et al., 2003). Although FAK protein expression remained constant in this study, elevated levels of phosphorylated FAK were found in carcinoma samples.
Entity name
Male genital tract cancer
FAK has been linked with aggressive tumor behavior in models of androgen-independent prostate cancer (Johnson et al., 2008). An early study comparing normal and hyperplastic prostatic tissue with localized and advanced prostate cancers demonstrated increased levels of total and activated FAK in more advanced disease (Tremblay et al., 1996). Association of FAK with paxillin and p50csk was noted in cases of metastatic cancer. Rovin et al. (2002) described increased FAK expression in pre-malignant lesions that was maintained at different stages of tumor progression. A study by Zheng et al. (1999) proposed that the migratory behavior of prostate cancer cells is related to the de novo expression of alphaVbeta3 integrin with signaling through FAK.
Entity name
Genito-urinary tract cancer
Increased levels of FAK and paxillin mRNA transcript have been noted in metastasizing renal carcinoma cell lines in comparison with normal renal cortex epithelial cells (Jenq et al., 1996). FAK/Src signaling was also demonstrated to be relevant to the aggressive behavior of bladder carcinoma cells in vitro, and inhibition of the phosphatase HD-PTP resulted in an enhanced FAK phosphorylation and increased cell motility (Mariotti et al., 2009).
Entity name
Skin cancer
Preclinical studies have implicated FAK with the promotion of an aggressive melanoma phenotype through its effects on invasion and migration (Hess et al., 2005; Hess and Hendrix 2006; Smit et al., 2007; Kaneda et al., 2008; Sun et al., 2009). FAK also has importance early in the metastatic dissemination of melanoma cells (Abdel-Ghany et al., 2002). A study by Smith et al. (2005) demonstrated that downregulation of FAK by antisense oligonucleotide sensitizes melanoma cells to 5-fluorouracil treatment. A preliminary clinical report suggests that FAK may function as a universal tumor-associated antigen that could be exploited for cancer immunotherapy including melanoma (Kobayashi et al., 2009). A recent study by Trimmer et al. (2010) reported reduced levels of caveolin-1 in clinical metastases of melanoma as well as in highly metastatic melanoma cell lines. They demonstrated that caveolin-1 expression in B16F10 melanoma cells promotes cell proliferation while suppressing invasion and migration via FAK/Src.
McLean et al. (2004) demonstrated a role for FAK in the malignant progression from papilloma to squamous cell carcinoma in a transgenic mouse model combined with chemical carcinogenesis. No effect of the FAK deletion was noted on wound re-epithelialization.
Entity name
Soft tissues, bone and hemato-lymphoid tissues
Yui et al. (2010) developed a highly metastatic osteosarcoma cell line through in vivo selection which, in comparison with the parental line, demonstrated higher levels of activated FAK and cdc42. Hanada et al. (2005) showed localization of phosphorylated FAK at the infiltrative edge in a three dimensional culture model using invasive murine fibrosarcoma cells. In the same study, expression of FAK-related non-kinase (FRNK) inhibited experimental metastases in syngenic mice without significant effects on primary tumor growth. In a study on bone metastasis, the dual FAK/Pyk2 inhibitor PF-271 suppressed the growth of experimental intra-tibial tumors in rats and restored tumor-induced bone loss (Bagi et al., 2008).
Immunohistochemical analysis of normal and neoplastic hemato-lymphoid tissues demonstrated FAK staining in B cells of the germinal center, marginal and mantle zones (Ozkal et al., 2009). Corresponding staining was present in most B-cell lymphomas while T-cell lymphomas were predominantly negative. Neoplastic cells of classical Hodgkins lymphoma were negative for FAK while those of lymphocyte-predominant Hodgkins lymphoma were positive in the same study.
A study of 60 primary acute myeloid leukemia samples demonstrated FAK transcript and protein expression in 48% cases and Pyk2 expression in 81% cases (Recher et al., 2004). FAK-positive acute myeloid leukemia cells displayed a higher migratory efficiency and lower sensitivity to chemotherapy. FAK expression positively correlated with white blood count at diagnosis, death rate and median survival.
Entity name
Non-neoplastic disorders
Shahrara et al. (2007) reported on the elevated expression of phosphorylated FAK, Pyk2 and other signaling molecules, in synovial tissues of patients with rheumatoid or osteoarthritis. They postulated that FAK signaling may be important for the recruitment of inflammatory cells into susceptible joints and required to promote the disease process.
Chen et al. (2001) found that keratinocytes from patients with psoriasis have elevated levels of phosphorylated FAK and concluded that integrin/FAK signaling contributes to a pre-activation of uninvolved keratinocytes that predisposes to the development of psoriatic plaques in response to certain stimuli.
FAK has a role in the development of the cardiovascular system since FAK-null mice are embryonically lethal with phenotypic abnormalities approximating those seen in human congenital heart defects (Vadali et al., 2007). FAK also appears to be involved cardiac hypertrophy and heart failure through its involvement in the cardiac response to biochemical stress and hypertrophic agonists. The relevance of FAK to cardiac physiology likely differs with the cellular context. Although FAK activation has been suggested to accelerate function deterioration of an overloaded heart, selective FAK deletion in cardiomyoctes has also been associated with maladaptive cardiac remodeling (Franchini et al., 2009).
FAK appears to be essential for normal glucose transport and glycogen synthesis due to cross talk between integrin and insulin signaling pathways (Huang et al., 2002; Huang et al., 2006). FAK has also been implicated in hyperglycemia-related vascular complications in Diabetes mellitus (Mori et al., 2002). Two independent studies reported on increased levels of activated FAK in the glomeruli from diabetic rats that could be abrogated by insulin treatment (Clark et al., 1995; Shikano et al., 1996).
FAK signaling has been implicated with non-neoplastic renal disease. Holzapfel et al. (2007) documented a role for FAK during restoration of tubular integrity in renal ischemia and reperfusion, and an earlier study by Morino et al. (1999) indicated activated FAK-signaling during the development and progression of autoimmune-mediated nephritis in an animal model.


Pubmed IDLast YearTitleAuthors
122211242002Regulation of focal adhesion kinase by a novel protein inhibitor FIP200.Abbi S et al
121106802002Focal adhesion kinase activated by beta(4) integrin ligation to mCLCA1 mediates early metastatic growth.Abdel-Ghany M et al
84222391993Expression of an N-terminally truncated form of human focal adhesion kinase in brain.André E et al
121341612002Src-induced de-regulation of E-cadherin in colon cancer cells requires integrin signalling.Avizienyte E et al
183482982008Dual focal adhesion kinase/Pyk2 inhibitor has positive effects on bone tumors: implications for bone metastases.Bagi CM et al
146422752003FAK deficiency in cells contributing to the basal lamina results in cortical abnormalities resembling congenital muscular dystrophies.Beggs HE et al
198858612010Inhibition of focal adhesion kinase and src increases detachment and apoptosis in human neuroblastoma cell lines.Beierle EA et al
76155491995Characterization of tyrosine phosphorylation of paxillin in vitro by focal adhesion kinase.Bellis SL et al
163910032006Endothelial FAK is essential for vascular network stability, cell survival, and lamellipodial formation.Braren R et al
183498462008Involvement of focal adhesion kinase in cellular invasion of head and neck squamous cell carcinomas via regulation of MMP-2 expression.Canel M et al
204314212010Evaluation of the clinical significance of focal adhesion kinase and SRC expression in human pancreatic ductal adenocarcinoma.Chatzizacharias NA et al
118865202001Basal keratinocytes from uninvolved psoriatic skin exhibit accelerated spreading and focal adhesion kinase responsiveness to fibronectin.Chen G et al
79378531994Association of focal adhesion kinase with its potential substrate phosphatidylinositol 3-kinase.Chen HC et al
118397722002Purification of pseudopodia from polarized cells reveals redistribution and activation of Rac through assembly of a CAS/Crk scaffold.Cho SY et al
179497122008TGFbeta-induced EMT requires focal adhesion kinase (FAK) signaling.Cicchini C et al
86901641995Increased phosphorylation of focal adhesion kinase in diabetic rat kidney glomeruli.Clark S et al
169021792006Myocyte-restricted focal adhesion kinase deletion attenuates pressure overload-induced hypertrophy.DiMichele LA et al
206210362010Expression of focal adhesion kinase and phosphorylated focal adhesion kinase in human gliomas is associated with unfavorable overall survival.Ding L et al
116026052001Reduced cell migration and disruption of the actin cytoskeleton in calpain-deficient embryonic fibroblasts.Dourdin N et al
151698992004FERM domain interaction promotes FAK signaling.Dunty JM et al
151185932004Focal adhesion kinase gene silencing promotes anoikis and suppresses metastasis of human pancreatic adenocarcinoma cells.Duxbury MS et al
158950762005Microtubule-induced focal adhesion disassembly is mediated by dynamin and focal adhesion kinase.Ezratty EJ et al
77669951995Mapping of the focal adhesion kinase (Fadk) gene to mouse chromosome 15 and human chromosome 8.Fiedorek FT Jr et al
192192962009Focal adhesion kinase signaling in cardiac hypertrophy and failure.Franchini KG et al
87078561996Control of adhesion-dependent cell survival by focal adhesion kinase.Frisch SM et al
152462152004Focal adhesion kinase is overexpressed in hepatocellular carcinoma and can be served as an independent prognostic factor.Fujii T et al
164250852006Clinical significance of focal adhesion kinase in resectable pancreatic cancer.Furuyama K et al
198230582009Expression of focal adhesion kinase in patients with endometrial cancer: a clinicopathologic study.Gabriel B et al
166388552006Weak expression of focal adhesion kinase (pp125FAK) in patients with cervical cancer is associated with poor disease outcome.Gabriel B et al
189879972009Expression and clinical significance of focal adhesion kinase in the two distinct histological types, intestinal and diffuse, of human gastric adenocarcinoma.Giaginis CT et al
195219852009FAK overexpression and p53 mutations are highly correlated in human breast cancer.Golubovskaya VM et al
154553822005Differential expression of protease activated receptor 1 (Par1) and pY397FAK in benign and malignant human ovarian tissue samples.Grisaru-Granovsky S et al
13796991992Regulation of focal adhesion-associated protein tyrosine kinase by both cellular adhesion and oncogenic transformation.Guan JL et al
175267302007Conditional deletion of focal adhesion kinase leads to defects in ventricular septation and outflow tract alignment.Hakim ZS et al
169145802006Focal adhesion kinase targeting using in vivo short interfering RNA delivery in neutral liposomes for ovarian carcinoma therapy.Halder J et al
163615722005Focal adhesion kinase silencing augments docetaxel-mediated apoptosis in ovarian cancer cells.Halder J et al
180068432007Therapeutic efficacy of a novel focal adhesion kinase inhibitor TAE226 in ovarian carcinoma.Halder J et al
163201112005Focal adhesion kinase is activated in invading fibrosarcoma cells and regulates metastasis.Hanada M et al
15288521992Focal adhesion protein-tyrosine kinase phosphorylated in response to cell attachment to fibronectin.Hanks SK et al
86629211996p130Cas, a substrate associated with v-Src and v-Crk, localizes to focal adhesions and binds to focal adhesion kinase.Harte MT et al
124566362002FRNK blocks v-Src-stimulated invasion and experimental metastases without effects on cell motility or growth.Hauck CR et al
201851622010Decreased expression of focal adhesion kinase is associated with a poor prognosis in extrahepatic bile duct carcinoma.Hayashi A et al
117994012002The focal adhesion targeting (FAT) region of focal adhesion kinase is a four-helix bundle that binds paxillin.Hayashi I et al
1972921520093D cell cultures of human head and neck squamous cell carcinoma cells are radiosensitized by the focal adhesion kinase inhibitor TAE226.Hehlgans S et al
165521812006Focal adhesion kinase signaling and the aggressive melanoma phenotype.Hess AR et al
162670082005Focal adhesion kinase promotes the aggressive melanoma phenotype.Hess AR et al
213212102011Endothelial focal adhesion kinase mediates cancer cell homing to discrete regions of the lungs via E-selectin up-regulation.Hiratsuka S et al
175495122007Role of focal adhesion kinase (FAK) in renal ischaemia and reperfusion.Holzapfel K et al
189740652008Apigenin inhibited migration and invasion of human ovarian cancer A2780 cells through focal adhesion kinase.Hu XW et al
118097462002Focal adhesion kinase (FAK) regulates insulin-stimulated glycogen synthesis in hepatocytes.Huang D et al
165747952006Reduced expression of focal adhesion kinase disrupts insulin action in skeletal muscle cells.Huang D et al
75661541995Reduced cell motility and enhanced focal adhesion contact formation in cells from FAK-deficient mice.Ilić D et al
183030502008FAK, PDZ-RhoGEF and ROCKII cooperate to regulate adhesion movement and trailing-edge retraction in fibroblasts.Iwanicki MP et al
170963712007FAK phosphorylation at Ser-843 inhibits Tyr-397 phosphorylation, cell spreading and migration.Jacamo R et al
90230461996Integrin expression on cell adhesion function and up-regulation of P125FAK and paxillin in metastatic renal carcinoma cells.Jenq W et al
189229792008Focal adhesion kinase controls aggressive phenotype of androgen-independent prostate cancer.Johnson TR et al
145007122003PIAS1-mediated sumoylation of focal adhesion kinase activates its autophosphorylation.Kadaré G et al
186064902008Mutation of Y925F in focal adhesion kinase (FAK) suppresses melanoma cell proliferation and metastasis.Kaneda T et al
21103611990Monoclonal antibodies to individual tyrosine-phosphorylated protein substrates of oncogene-encoded tyrosine kinases.Kanner SB et al
154833492004Increased expression of focal adhesion kinase in thyroid cancer: immunohistochemical study.Kim SJ et al
189417422009Focal adhesion kinase as an immunotherapeutic target.Kobayashi H et al
180566292007Mammary epithelial-specific disruption of the focal adhesion kinase blocks mammary tumor progression.Lahlou H et al
158612142005High focal adhesion kinase expression in invasive breast carcinomas is associated with an aggressive phenotype.Lark AL et al
211596352010Conditional deletion of the focal adhesion kinase FAK alters remodeling of the blood-brain barrier in glioma.Lee J et al
211799442010RNA interference-mediated silencing of focal adhesion kinase inhibits growth of human colon carcinoma xenograft in nude mice.Lei K et al
154947342004Activation of FAK and Src are receptor-proximal events required for netrin signaling.Li W et al
155647942004Upregulation of focal adhesion kinase (FAK) expression in ductal carcinoma in situ (DCIS) is an early event in breast tumorigenesis.Lightfoot HM Jr et al
182069652008Nuclear FAK promotes cell proliferation and survival through FERM-enhanced p53 degradation.Lim ST et al
186489072008Extended survival of Pyk2 or FAK deficient orthotopic glioma xenografts.Lipinski CA et al
154947322004Netrin requires focal adhesion kinase and Src family kinases for axon outgrowth and attraction.Liu G et al
119099672002Structural insight into the mechanisms of targeting and signaling of focal adhesion kinase.Liu G et al
155363342004Focal adhesion kinase overexpression in endometrial neoplasia.Livasy CA et al
191475592009Mammary epithelial-specific ablation of the focal adhesion kinase suppresses mammary tumorigenesis by affecting mammary cancer stem/progenitor cells.Luo M et al
111608182001Serine phosphorylation of focal adhesion kinase in interphase and mitosis: a possible role in modulating binding to p130(Cas).Ma A et al
188350892009Inhibition of T24 human bladder carcinoma cell migration by RNA interference suppressing the expression of HD-PTP.Mariotti M et al
156018182004Specific deletion of focal adhesion kinase suppresses tumor formation and blocks malignant progression.McLean GW et al
204053492010Evaluation of FAK and Src expression in human benign and malignant thyroid lesions.Michailidi C et al
211195982011Ligand-independent activation of c-Met by fibronectin and α(5)β(1)-integrin regulates ovarian cancer invasion and metastasis.Mitra AK et al
156880672005Focal adhesion kinase: in command and control of cell motility.Mitra SK et al
166829562006Intrinsic FAK activity and Y925 phosphorylation facilitate an angiogenic switch in tumors.Mitra SK et al
146753482003The expression and tyrosine phosphorylation of E-cadherin/catenin adhesion complex, and focal adhesion kinase in invasive cervical carcinomas.Moon HS et al
118723702002Hyperglycemia-induced alteration of vascular smooth muscle phenotype.Mori S et al
104572171999Glomerular overexpression and increased tyrosine phosphorylation of focal adhesion kinase p125FAK in lupus-prone MRL/MP-lpr/lpr mice.Morino N et al
208025172010DNA copy number aberrations in small-cell lung cancer reveal activation of the focal adhesion pathway.Ocak S et al
126735582003Focal adhesion kinase as a marker of malignant phenotype in breast and cervical carcinomas.Oktay MH et al
180709122007Regulation of lamellipodial persistence, adhesion turnover, and motility in macrophages by focal adhesion kinase.Owen KA et al
77963991995Overexpression of the focal adhesion kinase (p125FAK) in invasive human tumors.Owens LV et al
196479482009Focal adhesion kinase (FAK) expression in normal and neoplastic lymphoid tissues.Ozkal S et al
147648792004Localized stabilization of microtubules by integrin- and FAK-facilitated Rho signaling.Palazzo AF et al
192017552009Role of focal adhesion kinase Ser-732 phosphorylation in centrosome function during mitosis.Park AY et al
208697482010Focal adhesion kinase (FAK) gene amplification and its clinical implications in gastric cancer.Park JH et al
163745172006Inactivation of focal adhesion kinase in cardiomyocytes promotes eccentric cardiac hypertrophy and fibrosis in mice.Peng X et al
184486752008Cardiac developmental defects and eccentric right ventricular hypertrophy in cardiomyocyte focal adhesion kinase (FAK) conditional knockout mice.Peng X et al
187738902008Focal adhesion kinase regulates cell-cell contact formation in epithelial cells via modulation of Rho.Playford MP et al
74798641995Interaction between focal adhesion kinase and Crk-associated tyrosine kinase substrate p130Cas.Polte TR et al
206973462010MUC4 mucin-induced epithelial to mesenchymal transition: a novel mechanism for metastasis of human ovarian cancer cells.Ponnusamy MP et al
188458372008Mammary epithelial-specific disruption of focal adhesion kinase retards tumor formation and metastasis in a transgenic mouse model of human breast cancer.Provenzano PP et al
191479812009Ras- and PI3K-dependent breast tumorigenesis in mice and humans requires focal adhesion kinase signaling.Pylayeva Y et al
151263592004Expression of focal adhesion kinase in acute myeloid leukemia is associated with enhanced blast migration, increased cellularity, and poor prognosis.Recher C et al
154947332004Focal adhesion kinase in netrin-1 signaling.Ren XR et al
122427272002Expression of focal adhesion kinase in normal and pathologic human prostate tissues.Rovin JD et al
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157435002005High expression of focal adhesion kinase (p125FAK) in node-negative breast cancer is related to overexpression of HER-2/neu and activated Akt kinase but does not predict outcome.Schmitz KJ et al
194580652009Targeting focal adhesion kinase with dominant-negative FRNK or Hsp90 inhibitor 17-DMAG suppresses tumor growth and metastasis of SiHa cervical xenografts.Schwock J et al
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159678142005Conditional knockout of focal adhesion kinase in endothelial cells reveals its role in angiogenesis and vascular development in late embryogenesis.Shen TL et al
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177247182007Osteonectin downregulates E-cadherin, induces osteopontin and focal adhesion kinase activity stimulating an invasive melanoma phenotype.Smit DJ et al
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101976431999Prostatic carcinoma cell migration via alpha(v)beta3 integrin is modulated by a focal adhesion kinase pathway.Zheng DQ et al
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Other Information

Locus ID:

NCBI: 5747
MIM: 600758
HGNC: 9611
Ensembl: ENSG00000169398


dbSNP: 5747
ClinVar: 5747
TCGA: ENSG00000169398


Gene IDTranscript IDUniprot

Expression (GTEx)



PathwaySourceExternal ID
ErbB signaling pathwayKEGGko04012
Axon guidanceKEGGko04360
VEGF signaling pathwayKEGGko04370
Focal adhesionKEGGko04510
Leukocyte transendothelial migrationKEGGko04670
Regulation of actin cytoskeletonKEGGko04810
Small cell lung cancerKEGGko05222
ErbB signaling pathwayKEGGhsa04012
Axon guidanceKEGGhsa04360
VEGF signaling pathwayKEGGhsa04370
Focal adhesionKEGGhsa04510
Leukocyte transendothelial migrationKEGGhsa04670
Regulation of actin cytoskeletonKEGGhsa04810
Pathways in cancerKEGGhsa05200
Small cell lung cancerKEGGhsa05222
Chemokine signaling pathwayKEGGko04062
Chemokine signaling pathwayKEGGhsa04062
Bacterial invasion of epithelial cellsKEGGko05100
Bacterial invasion of epithelial cellsKEGGhsa05100
Transcriptional misregulation in cancerKEGGko05202
Transcriptional misregulation in cancerKEGGhsa05202
PI3K-Akt signaling pathwayKEGGhsa04151
PI3K-Akt signaling pathwayKEGGko04151
Proteoglycans in cancerKEGGhsa05205
Proteoglycans in cancerKEGGko05205
Immune SystemREACTOMER-HSA-168256
Innate Immune SystemREACTOMER-HSA-168249
Fcgamma receptor (FCGR) dependent phagocytosisREACTOMER-HSA-2029480
Regulation of actin dynamics for phagocytic cup formationREACTOMER-HSA-2029482
DAP12 interactionsREACTOMER-HSA-2172127
DAP12 signalingREACTOMER-HSA-2424491
RAF/MAP kinase cascadeREACTOMER-HSA-5673001
Fc epsilon receptor (FCERI) signalingREACTOMER-HSA-2454202
FCERI mediated MAPK activationREACTOMER-HSA-2871796
Cytokine Signaling in Immune systemREACTOMER-HSA-1280215
Signaling by InterleukinsREACTOMER-HSA-449147
Interleukin-2 signalingREACTOMER-HSA-451927
Interleukin receptor SHC signalingREACTOMER-HSA-912526
Interleukin-3, 5 and GM-CSF signalingREACTOMER-HSA-512988
Platelet activation, signaling and aggregationREACTOMER-HSA-76002
Platelet Aggregation (Plug Formation)REACTOMER-HSA-76009
Integrin alphaIIb beta3 signalingREACTOMER-HSA-354192
GRB2:SOS provides linkage to MAPK signaling for IntegrinsREACTOMER-HSA-354194
p130Cas linkage to MAPK signaling for integrinsREACTOMER-HSA-372708
Signal TransductionREACTOMER-HSA-162582
Signaling by EGFRREACTOMER-HSA-177929
GRB2 events in EGFR signalingREACTOMER-HSA-179812
SHC1 events in EGFR signalingREACTOMER-HSA-180336
Signaling by Insulin receptorREACTOMER-HSA-74752
Insulin receptor signalling cascadeREACTOMER-HSA-74751
IRS-mediated signallingREACTOMER-HSA-112399
SOS-mediated signallingREACTOMER-HSA-112412
Signalling by NGFREACTOMER-HSA-166520
NGF signalling via TRKA from the plasma membraneREACTOMER-HSA-187037
Signalling to ERKsREACTOMER-HSA-187687
Signalling to RASREACTOMER-HSA-167044
Signalling to p38 via RIT and RINREACTOMER-HSA-187706
Prolonged ERK activation eventsREACTOMER-HSA-169893
Frs2-mediated activationREACTOMER-HSA-170968
ARMS-mediated activationREACTOMER-HSA-170984
Signaling by PDGFREACTOMER-HSA-186797
Downstream signal transductionREACTOMER-HSA-186763
Signaling by VEGFREACTOMER-HSA-194138
VEGFR2 mediated cell proliferationREACTOMER-HSA-5218921
Signaling by SCF-KITREACTOMER-HSA-1433557
MAPK family signaling cascadesREACTOMER-HSA-5683057
MAPK1/MAPK3 signalingREACTOMER-HSA-5684996
Signaling by Rho GTPasesREACTOMER-HSA-194315
RHO GTPase EffectorsREACTOMER-HSA-195258
RHO GTPases Activate WASPs and WAVEsREACTOMER-HSA-5663213
Signaling by GPCRREACTOMER-HSA-372790
Gastrin-CREB signalling pathway via PKC and MAPKREACTOMER-HSA-881907
Signaling by Type 1 Insulin-like Growth Factor 1 Receptor (IGF1R)REACTOMER-HSA-2404192
IGF1R signaling cascadeREACTOMER-HSA-2428924
IRS-related events triggered by IGF1RREACTOMER-HSA-2428928
Signaling by LeptinREACTOMER-HSA-2586552
Cell-Cell communicationREACTOMER-HSA-1500931
Signal regulatory protein (SIRP) family interactionsREACTOMER-HSA-391160
Programmed Cell DeathREACTOMER-HSA-5357801
Apoptotic execution phaseREACTOMER-HSA-75153
Apoptotic cleavage of cellular proteinsREACTOMER-HSA-111465
Developmental BiologyREACTOMER-HSA-1266738
Axon guidanceREACTOMER-HSA-422475
NCAM signaling for neurite out-growthREACTOMER-HSA-375165
Netrin-1 signalingREACTOMER-HSA-373752
DCC mediated attractive signalingREACTOMER-HSA-418885
Netrin mediated repulsion signalsREACTOMER-HSA-418886
EPH-Ephrin signalingREACTOMER-HSA-2682334
EPHA-mediated growth cone collapseREACTOMER-HSA-3928663
EPHB-mediated forward signalingREACTOMER-HSA-3928662
Endocrine resistanceKEGGko01522
Endocrine resistanceKEGGhsa01522
RET signalingREACTOMER-HSA-8853659
Signaling by METREACTOMER-HSA-6806834
MET promotes cell motilityREACTOMER-HSA-8875878
MET activates PTK2 signalingREACTOMER-HSA-8874081
Fluid shear stress and atherosclerosisKEGGko05418
Fluid shear stress and atherosclerosisKEGGhsa05418

Protein levels (Protein atlas)

Not detected


Pubmed IDYearTitleCitations
198264152009Matrix density-induced mechanoregulation of breast cell phenotype, signaling and gene expression through a FAK-ERK linkage.249
125318882003Myofibroblast differentiation by transforming growth factor-beta1 is dependent on cell adhesion and integrin signaling via focal adhesion kinase.232
273765762016Targeting focal adhesion kinase renders pancreatic cancers responsive to checkpoint immunotherapy.192
182069652008Nuclear FAK promotes cell proliferation and survival through FERM-enhanced p53 degradation.188
156578752005Polymorphisms in the tyrosine kinase 2 and interferon regulatory factor 5 genes are associated with systemic lupus erythematosus.182
197363512009Recurrent rearrangements in synaptic and neurodevelopmental genes and shared biologic pathways in schizophrenia, autism, and mental retardation.151
209669712010The FERM domain: organizing the structure and function of FAK.125
191479812009Ras- and PI3K-dependent breast tumorigenesis in mice and humans requires focal adhesion kinase signaling.123
127001322003Focal adhesion kinase signaling activities and their implications in the control of cell survival and motility.121
151662382004Focal adhesion kinase is upstream of phosphatidylinositol 3-kinase/Akt in regulating fibroblast survival in response to contraction of type I collagen matrices via a beta 1 integrin viability signaling pathway.121


Joerg Schwock ; Neesha Dhani

PTK2 (PTK2 protein tyrosine kinase 2)

Atlas Genet Cytogenet Oncol Haematol. 2011-03-01

Online version: