Written | 2016-03 | Barnabas Nyesiga, Anette Gjörloff Wingren |
Department of Biomedical Science, Health and Society, Malmö University, Malmö, Sweden. anette.gjorloff-wingren@mah.se |
This article is an update of : |
2002-02 | Jean-Loup Huret | |
Genetics, Dept Medical Information, University of Poitiers, CHU Poitiers Hospital, F-86021 Poitiers, France |
Identity |
Alias (NCBI) | P72-Syk | Tyrosine-Protein Kinase SYK | EC 2.7.10.2 | EC 2.7.10 |
HGNC (Hugo) | SYK |
HGNC Previous name | spleen tyrosine kinase |
LocusID (NCBI) | 6850 |
Atlas_Id | 394 |
Location | 9q22.2 [Link to chromosome band 9q22] |
Location_base_pair | Starts at 90801819 and ends at 90898549 bp from pter ( according to GRCh38/hg38-Dec_2013) [Mapping SYK.png] |
![]() | |
Figure 1. Mapping of SYK gene on chromosome 9q22.2 (from GeneCards Syk gene). | |
Fusion genes (updated 2017) | Data from Atlas, Mitelman, Cosmic Fusion, Fusion Cancer, TCGA fusion databases with official HUGO symbols (see references in chromosomal bands) |
DNMT3B (20q11.21) / SYK (9q22.2) | ETV6 (12p13.2) / SYK (9q22.2) | ITK (5q33.3) / SYK (9q22.2) | |
SYK (9q22.2) / ETV6 (12p13.2) | SYK (9q22.2) / ITK (5q33.3) | SYK (9q22.2) / SYK (9q22.2) | |
DNA/RNA |
Description | The spleen tyrosine kinase (SYK) gene encodes a member of the family of non-receptor type Tyr protein kinases (http://www.genecards.org/cgi-bin/carddisp.pl?gene=SYK). The cDNA clone encoding porcine SYK was identified by Taniguchi et al (Taniguchi 1991; Yamada 1993), and thereafter the SYK cDNA for mouse and human, respectively, was cloned (Hutchcroft 1991; Hutchcroft 1992; Müller 1994; Ku 1994). Initially, a smaller porcine SYK protein product was purified and was found to be proteolytically cleaved from the mature SYK protein (Kobayashi 1990). The PTK72 was at the same time found to be identical with the cloned SYK (LePrince 1993; Law 1994). |
Transcription | The transcript encodes 635 amino acids with a mass of 72,066 Da. Two isoforms have been described, isoform long (L) and isoform short (S) (http://www.uniprot.org/uniprot/P43405): Isoform 1 (full-length); Isoform 2 (283-305 missing) |
Protein |
Description | SYK is a 72 kDa non-receptor type protein tyrosine kinase (PTK) that contains two SRC homology 2 (SH2) domains, interdomains A and B, and a C-terminal kinase domain (Fig. 2). SYK was initially shown to be expressed in lymphocytes and associated with the IgM and IgD receptor complexes in B cells (Taniguchi 1991; Hutchcroft 1992). The requirement for Src-PTKs associated with the B cell receptor (BCR) for phosphorylation of SYK was investigated early, and was shown to enhance the activity of SYK (Kurosaki 1994). The PTK ZAP70 was cloned in T lymphocytes and shown to be homologous to SYK (Chan 1992). An alternatively spliced form of SYK also exists, missing 23 amino acids from interdomain A (Sada 2001). The topology of the N-terminal part of SYK is similar to its counterpart ZAP70 as revealed by the crystal structure (Narula 1995; Hatada 1995). In 1998, Fütterer et al presented the crystal structure of the tandem SH2 domain of SYK complexed with a dually phosphorylated ITAM peptide (Fütterer 1998). The tandem SH2 domains selectively bind to diphosphorylated immunoreceptor tyrosine based activating motifs (ITAM) of the cytoplasmic region of the BCR (Sada 2001). The crystal structure of a full-length version of ZAP70 has given a greater understanding of the activation process for both SYK and Zap-70 (Deindl 2007). Atwell et al determined the structure of the unphosphorylated form of the SYK kinase catalytic domain (SYK-KD) in order to understand the molecular mechanism responsible for its enzymatic activity (Atwell 2004). The SYK kinase domain has a subdomain structure composed of a largely β-sheet N-terminal lobe, a largely α–helical C-terminal lobe, with the active site being sandwiched between the two lobes. The N-terminal lobe consists of a five-stranded β -sheet plus a single α –helix. The larger C-terminal lobe is predominantly α –helical with three short β -strands: one at the hinge region and two between the activation loop and the main body of the C-lobe. From the structure of the SYK kinase domain it was deduced that the SYK catalytic activity does not require activation loop phosphorylation. SYK have multiple sites of phosphorylation which both regulate activity and serve as docking motifs for other proteins (Sada 2001). Phosphorylation sites include Tyr-348 and Tyr-352 within the SH2-linker region (Brdicka 2005), Tyr-525 and Tyr-526 within the activation loop of the kinase domain (Zhang 2000), Tyr-630 in the C terminus of SYK, and others (Kulathu 2008; Tsang 2008; and reviewed by Sada 2001). In B cells, the phosphorylation of two tyrosines within the ITAM leads to the physical recruitment of SYK to the site of the clustered receptor in an interaction mediated by its tandem pair of SH2 domains (reviewed in Geahlen 2009). Shortly following BCR engagement, SYK that has been recruited to the receptor becomes phosphorylated on multiple tyrosines through both autophosphorylation and phosphorylation by Lyn. |
![]() | |
Figure 2. Schematic structure of spleen tyrosine kinase (SYK) protein (adopted from Pamuk et al 2010). The protein includes two tandem SH2 domains and a tyrosine kinase domain. Between the two SH2 domains is interdomain A while interdomain B is located between the tyrosine kinase domain and C-terminal domain. ITAM, immunoreceptor tyrosine-based activation motif; SH2, Src homology 2. | |
Expression | SYK expression in hematopoietic cells has been extensively determined by studying SYK as an effector of BCR signalling. Turner and co-workers found that after BCR activation, SYK-dependent signaling pathways regulate the clonal expansion, differentiation, or apoptosis of B cells (Turner 2000). Most of the cells of the hematopoietic system express SYK, but the PTK is also expressed at lower levels in some epithelial cells, fibroblasts, hepatocytes, vascular smooth muscle cells, endothelial cells and neuronal cells where it mediates various responses including adipogenesis, cell division, tumor suppression, ERK activation and neuronal differentiation (Turner 2000; Yanagi 2001; Zhou 2006; Tohyama 2009; Geahlen 2009; Mócsai 2010; Krisenko 2015). In hepatocytes, after the use of the SYK-selective inhibitor piceatannol, it was indicated that SYK is necessary for mitogen activated protein kinase (MAPK) activation by G-protein coupled receptors in this cell type (Tsuchida 2000). Additionally, SYK expression has also been observed in normal human breast tissue, benign lesions and low-tumourigenic breast cancer cell lines (Coopman 2000). |
Localisation | SYK is an intracellular PTK, known to function at the plasma membrane, where the receptors to which it is recruited are located (Zhou 2006). In lymphoid and epithelial cells, SYK has been found to reside in both the nucleus and cytoplasm (Ma 2001; Wang 2003; Wang 2004). The expression and localization of SYK in the nucleus of breast cancer cells have been correlated with the repression of invasive tumor growth (Wang 2003). |
Function | The SYK protein is known to have an important role in adaptive immune receptor signalling with recent reports indicating its mediation of other diverse biological functions, including cellular adhesion, innate immune recognition, osteoclast maturation, platelet activation and vascular development (Mócsai 2010). The protein is also involved in coupling activated immunoreceptors to downstream signaling events that mediate diverse cellular responses, including proliferation, differentiation, and phagocytosis. SYK plays a critical role in the transition of pro-B cells into pre-B cells (Turner 1995). SYK is greatly involved in signal transduction initiated by the classic immunoreceptors, including BCRs, Fc receptors, and the activating natural killer receptors (Tohyama 2009; Berton 2005; Crowley 1997). SYK is associated mainly with ITAM dependent pathways and affects early development and activation of various cells including B cells, mast cell degranulation, neutrophil and macrophage phagocytosis, as well as platelet activation (Zhou 2006; Tohyama 2009; Mócsai 2010). SYK-mediated phosphorylation of various adaptor proteins leads to the activation of downstream pathways that execute phagocytosis. SYK is important in complement-mediated phagocytosis resulting from the binding of C3bi-coated particles to complement receptor 3 (Tohyama 2009; Tohyama 2006). SYK is known to play a major role in the development of signal transduction events initiated after high-affinity IgE receptor (FCER1A) aggregation (Wong 2004; Matsubara 2006), mast cell activation, degranulation, and cytokine production (Matsubara 2006; Masuda 2008). It is anticipated that SYK activation coupled with platelet activation and aggregation may assist in lymphatic vessel development and their separation from blood vessels (Mócsai 2010, Turner 1995). SYK is claimed to have a role in osteoclast differentiation and osteoclast function (Tohyama 2009, Mócsai 2010). SYK has been found to have a major role in pre T-cell receptor (TCR) signalling. This is known to occur during the transition from the double negative 3 (DN3) to the DN4 stage of early thymocyte development (Palacios 2007). In vivo studies have shown that SYK is required for firm leukocyte adhesion to inflamed endothelium (Frommhold 2007) and development of vasculopathy reaction (Hirahashi 2006). The innate immune system uses pattern recognition receptors (PRRs) to detect pathogen-associated molecular patterns (PAMPs) and activate immune responses. SYK has been found to be a key component of these pathways and increased evidence points to the involvement of SYK-coupled PRRs in innate recognition of bacteria, with CLEC7A, CLEC6A and CLEC4E all implicated in sensing of mycobacterial PAMPs (Geijtenbeek 2009). SYK is presumably also involved in signalling PRR-mediated recognition of certain viruses. The role of ZAP70 in B cells have been investigated, but is poorly understood possibly due to the functional redundancy between SYK and ZAP70 (Fallah-Arani 2008). Toyabe et al displayed the ability of a T cell subpopulation to express high levels of SYK and partially compensate for loss of T-cell functions in patients with deficiency of ZAP70 (Toyabe 2001). |
Homology | Both ZAP-70 and SYK are dependent upon a Src-family protein tyrosine kinase for association with the phosphorylated zeta-chain. Thus, the differential expression of these kinases suggests the possibility of different roles for ZAP70 and SYK in TCR signaling and thymic development (Palacios 2007). Activation of PTKs is an important mechanism in the transduction of signals from multi-subunit immunoreceptors, including the B and T cell receptors for antigen and the widely distributed receptors for the Fc portion of immunoglobulins (Paolini 2001). ZAP70 is expressed in T cells, natural killer cells and thymocytes, whereas SYK is present in all hematopoietic cells. Both ZAP70 and SYK are reported to be activated after TCR stimulation. Nonetheless, ZAP70 activation is known to require presence of Lck or another associated Src family PTK, while SYK is independent of Lck to undergo phosphorylation (Chan 1994, Couture 1994, Kolanus 1993). Regardless of its presence in all thymocyte subsets, SYK expression is downregulated three- to fourfold in peripheral T cells and, contrary to ZAP70, SYK expression is 12- to 15-fold higher in peripheral B cells compared to peripheral T cells (Chan 1994). Another study showed functional homology in antigen receptor signaling by demonstrating that expression of ZAP70 in SYK-B cells reconstitutes BCR function (Kong 1995). Another feature that distinguish ZAP70 from SYK is its greater dependency on Src kinases for activation and its ability to phosphorylate and promote the auto-activation of the downstream MAPK p38 (reviewed in Au-Yeung 2009). |
Mutations |
Note | The development of B cells proceeds through a well-characterized set of stages defined by the extent of antigen receptor rearrangement and the expression of particular cell surface markers. When mice deficient for recombination-activating gene 1 (RAG1) were reconstituted with fetal liver from SYK-deficient embryos, the pool of pre-B cells formed was reduced. This suggests that SYK is required for the proper signalling from the pre-BCR to generate or maintain the pool of pre-B cells. Indeed, it has been shown that SYK is an essential transducer of BCR signals required for the transition of immature into recirculating B cells (Turner 2000). Moreover, SYK-deficient mice die due to embryonic and perinatal death (Turner 1995; Cheng 1995). |
Epigenetics | SYK can also be inactivated by epigenetic modifications (i.e. hypermethylation) |
Implicated in |
Note | |
Entity | t(5;9)(q33;q22) |
Disease | found in Peripheral T-cell lymphoma (Streubel et al. 2006). |
Hybrid/Mutated Gene | N-terminal ITK (bp 1-577) fused in frame with C-terminal SYK cDNA |
Entity | t(9;12)(q22;p12) |
Disease | found in a case of myelodysplastic syndrome (Kuno et al. 2001). |
Oncogenesis | ETV6-SYK is constituvely tyrosine phosphorylated |
Entity | Breast cancer |
Note | SYK mRNA and protein expression in a panel of well-characterized breast cancer cell lines, normal mammary gland tissue, and a normal breast epithelial cell line has been investigated by Coopman et al (Coopman 2000). They readily detected SYK expression in normal mammary tissue and epithelium, as well as in non-invasive breast carcinoma cell lines. SYK expression was however observed to be reduced or absent in the invasive breast tumor cell lines. Hypermethylation of the SYK locus during breast cancer progression was found to cause a loss of SYK protein expression in highly invasive and metastatic human mammary carcinomas (Coopman 2000,Yuan 2001). Moreover, Wang et al have shown that full-length SYK can enter the nucleus and thereby suppress invasion (Wang 2003). The sequences confined to a region of the SYK molecule near the junction of the linker B and catalytic domain were determined to be responsible for its distribution between the nucleus and cytoplasm (Zhou 2006). It was further demonstrated that the distribution of SYK between the nucleus and cytoplasm was regulated by signals sent downstream from the activated BCR and require the receptor-mediated activation of protein kinase C (PKC) and the induction of new protein synthesis. |
Entity | Colon carcinoma |
Note | Expression of the SYK gene in human colon carcinoma cells is known to be suppressed in a p53-dependent manner, an indication that loss of p53 function during tumorigenesis can lead to deregulation of SYK activity (Okamura 1999). As reviewed recently by Krisenko et al,the levels of SYK mRNA in many cancerous tissues, including colon, are higher than in normal corresponding tissue (Krisenko 2015). |
Entity | Gastric cancer |
Note | An inverse correlation between nuclear SYK and lymph node metastasis was observed in gastric cancer patients (Wang 2004). |
Entity | Ovarian cancer |
Note | Ovarian tumors of low malignant grade have low levels of SYK compared to aggressive grades, which have the highest levels (Prinos 2011). Interestingly, when SYK expression was silenced, anchorage-independent growth was inhibited, and apoptosis was induced in SYK-expressing ovarian cancer cells. |
Entity | Lung cancer |
Note | Primary tumors of small cell lung cancer (SCLC) was examined and found to express higher levels of SYK compared to normal alveolar epithelium (reviewed by Krisenko 2015). |
Entity | Chronic lymphocytic leukemia (CLL) |
Note | Both SYK and ZAP70 are present in CLL in B cells and may compete in facilitating BCR signaling (reviewed in Au-Yeung 2009). CLL fall into two classes, an indolent milder form and an aggressive form that is particularly dependent on SYK activity for survival (Buchner 2009). |
Entity | Diffuse large B-cell lymphoma (DLBCL) |
Note | DLBCL can exhibit tonic or chronic signaling from the BCR that results in constitutive phosphorylation of SYK on activation loop tyrosines (Chen 2008). In a study from 2011 by Cheng et al, 44% of DLBCL samples showed elevated levels of phosphorylated SYK (Cheng 2011). |
Entity | Follicular lymphoma (FL) |
Note | Constitutive activation of SYK has been reported in FL, were primary cells are hyperresponsive to BCR engagement as compared to nonmalignant B cells (Leseux 2006; Irish 2006). |
Entity | Mantle cell lymphoma (MCL) |
Note | Constitutive activation of SYK has been reported in MCL as well, with a frequent overexpression of SYK due to gene amplification in both cell lines and primary tumors (Rinaldi 2006). |
Entity | Marginal zone lymphoma (MZL) |
Note | Ruiz-Ballesteros reported upregulation of SYK in splenic MZL, potentially due to downregulation of microRNAs predicted to modulate SYK gene transcription (Ruiz-Ballesteros 2005). |
Entity | B cell acute lymphocytic leukemia (B-ALL) |
Note | B-ALL cells are derived from pro-B cells that lack pre-BCR or BCR complexes, but still these cells have elevated levels of constitutively active phosphorylated SYK (Perova 2014). |
Entity | Rheumatoid arthritis (RA) |
Note | It is likely that SYK is widely expressed in a range of haemopoietic cell lineages in RA synovium. Inhibition of Syk suppresses both inflammation and bone erosion in animal models of RA (Singh Najjar 2014). Indeed, Syk has been shown to be necessary for emerging pathology in several animal models of arthritis. |
Bibliography |
A novel mode of Gleevec binding is revealed by the structure of spleen tyrosine kinase |
Atwell S, Adams JM, Badger J, Buchanan MD, Feil IK, Froning KJ, Gao X, Hendle J, Keegan K, Leon BC, Müller-Dieckmann HJ, Nienaber VL, Noland BW, Post K, Rajashankar KR, Ramos A, Russell M, Burley SK, Buchanan SG |
J Biol Chem 2004 Dec 31;279(53):55827-32 |
PMID 15507431 |
The structure, regulation, and function of ZAP-70 |
Au-Yeung BB, Deindl S, Hsu LY, Palacios EH, Levin SE, Kuriyan J, Weiss A |
Immunol Rev 2009 Mar;228(1):41-57 |
PMID 19290920 |
Src and Syk kinases: key regulators of phagocytic cell activation |
Berton G, Mócsai A, Lowell CA |
Trends Immunol 2005 Apr;26(4):208-14 |
PMID 15797511 |
Intramolecular regulatory switch in ZAP-70: analogy with receptor tyrosine kinases |
Brdicka T, Kadlecek TA, Roose JP, Pastuszak AW, Weiss A |
Mol Cell Biol 2005 Jun;25(12):4924-33 |
PMID 15923611 |
ZAP-70: a 70 kd protein-tyrosine kinase that associates with the TCR zeta chain |
Chan AC, Iwashima M, Turck CW, Weiss A |
Cell 1992 Nov 13;71(4):649-62 |
PMID 1423621 |
Differential expression of ZAP-70 and Syk protein tyrosine kinases, and the role of this family of protein tyrosine kinases in TCR signaling |
Chan AC, van Oers NS, Tran A, Turka L, Law CL, Ryan JC, Clark EA, Weiss A |
J Immunol 1994 May 15;152(10):4758-66 |
PMID 8176201 |
ZAP-70 enhances IgM signaling independent of its kinase activity in chronic lymphocytic leukemia |
Chen L, Huynh L, Apgar J, Tang L, Rassenti L, Weiss A, Kipps TJ |
Blood 2008 Mar 1;111(5):2685-92 |
PMID 18048647 |
Syk tyrosine kinase required for mouse viability and B-cell development |
Cheng AM, Rowley B, Pao W, Hayday A, Bolen JB, Pawson T |
Nature 1995 Nov 16;378(6554):303-6 |
PMID 7477353 |
SYK inhibition and response prediction in diffuse large B-cell lymphoma |
Cheng S, Coffey G, Zhang XH, Shaknovich R, Song Z, Lu P, Pandey A, Melnick AM, Sinha U, Wang YL |
Blood 2011 Dec 8;118(24):6342-52 |
PMID 22025527 |
The Syk tyrosine kinase suppresses malignant growth of human breast cancer cells |
Coopman PJ, Do MT, Barth M, Bowden ET, Hayes AJ, Basyuk E, Blancato JK, Vezza PR, McLeskey SW, Mangeat PH, Mueller SC |
Nature 2000 Aug 17;406(6797):742-7 |
PMID 10963601 |
Activation of p56lck by p72syk through physical association and N-terminal tyrosine phosphorylation |
Couture C, Baier G, Oetken C, Williams S, Telford D, Marie-Cardine A, Baier-Bitterlich G, Fischer S, Burn P, Altman A, et al |
Mol Cell Biol 1994 Aug;14(8):5249-58 |
PMID 7518561 |
A critical role for Syk in signal transduction and phagocytosis mediated by Fcgamma receptors on macrophages |
Crowley MT, Costello PS, Fitzer-Attas CJ, Turner M, Meng F, Lowell C, Tybulewicz VL, DeFranco AL |
J Exp Med 1997 Oct 6;186(7):1027-39 |
PMID 9314552 |
Structural basis for the inhibition of tyrosine kinase activity of ZAP-70 |
Deindl S, Kadlecek TA, Brdicka T, Cao X, Weiss A, Kuriyan J |
Cell 2007 May 18;129(4):735-46 |
PMID 17512407 |
Redundant role for Zap70 in B cell development and activation |
Fallah-Arani F, Schweighoffer E, Vanes L, Tybulewicz VL |
Eur J Immunol 2008 Jun;38(6):1721-33 |
PMID 18465772 |
Spleen tyrosine kinase Syk is critical for sustained leukocyte adhesion during inflammation in vivo |
Frommhold D, Mannigel I, Schymeinsky J, Mocsai A, Poeschl J, Walzog B, Sperandio M |
BMC Immunol 2007 Nov 28;8:31 |
PMID 18045459 |
Structural basis for Syk tyrosine kinase ubiquity in signal transduction pathways revealed by the crystal structure of its regulatory SH2 domains bound to a dually phosphorylated ITAM peptide |
Fütterer K, Wong J, Grucza RA, Chan AC, Waksman G |
J Mol Biol 1998 Aug 21;281(3):523-37 |
PMID 9698567 |
Syk and pTyr'd: Signaling through the B cell antigen receptor |
Geahlen RL |
Biochim Biophys Acta 2009 Jul;1793(7):1115-27 |
PMID 19306898 |
Signalling through C-type lectin receptors: shaping immune responses |
Geijtenbeek TB, Gringhuis SI |
Nat Rev Immunol 2009 Jul;9(7):465-79 |
PMID 19521399 |
Molecular basis for interaction of the protein tyrosine kinase ZAP-70 with the T-cell receptor |
Hatada MH, Lu X, Laird ER, Green J, Morgenstern JP, Lou M, Marr CS, Phillips TB, Ram MK, Theriault K, et al |
Nature 1995 Sep 7;377(6544):32-8 |
PMID 7659156 |
Mac-1 signaling via Src-family and Syk kinases results in elastase-dependent thrombohemorrhagic vasculopathy |
Hirahashi J, Mekala D, Van Ziffle J, Xiao L, Saffaripour S, Wagner DD, Shapiro SD, Lowell C, Mayadas TN |
Immunity 2006 Aug;25(2):271-83 |
PMID 16872848 |
Association of the 72-kDa protein-tyrosine kinase PTK72 with the B cell antigen receptor |
Hutchcroft JE, Harrison ML, Geahlen RL |
J Biol Chem 1992 Apr 25;267(12):8613-9 |
PMID 1569106 |
Altered B-cell receptor signaling kinetics distinguish human follicular lymphoma B cells from tumor-infiltrating nonmalignant B cells |
Irish JM, Czerwinski DK, Nolan GP, Levy R |
Blood 2006 Nov 1;108(9):3135-42 |
PMID 16835385 |
Purification and characterization of a cytosolic protein-tyrosine kinase from porcine spleen |
Kobayashi T, Nakamura S, Taniguchi T, Yamamura H |
Eur J Biochem 1990 Mar 30;188(3):535-40 |
PMID 2331984 |
T cell activation by clustered tyrosine kinases |
Kolanus W, Romeo C, Seed B |
Cell 1993 Jul 16;74(1):171-83 |
PMID 8334702 |
Reconstitution of Syk function by the ZAP-70 protein tyrosine kinase |
Kong GH, Bu JY, Kurosaki T, Shaw AS, Chan AC |
Immunity 1995 May;2(5):485-92 |
PMID 7538440 |
Calling in SYK: SYK's dual role as a tumor promoter and tumor suppressor in cancer |
Krisenko MO, Geahlen RL |
Biochim Biophys Acta 2015 Jan;1853(1):254-63 |
PMID 25447675 |
Chromosomal location of the Syk and ZAP-70 tyrosine kinase genes in mice and humans |
Ku G, Malissen B, Mattei MG |
Immunogenetics 1994;40(4):300-2 |
PMID 8082894 |
The kinase Syk as an adaptor controlling sustained calcium signalling and B-cell development |
Kulathu Y, Hobeika E, Turchinovich G, Reth M |
EMBO J 2008 May 7;27(9):1333-44 |
PMID 18369315 |
Constitutive kinase activation of the TEL-Syk fusion gene in myelodysplastic syndrome with t(9;12)(q22;p12) |
Kuno Y, Abe A, Emi N, Iida M, Yokozawa T, Towatari M, Tanimoto M, Saito H |
Blood 2001 Feb 15;97(4):1050-5 |
PMID 11159536 |
Syk activation by the Src-family tyrosine kinase in the B cell receptor signaling |
Kurosaki T, Takata M, Yamanashi Y, Inazu T, Taniguchi T, Yamamoto T, Yamamura H |
J Exp Med 1994 May 1;179(5):1725-9 |
PMID 7513017 |
Molecular cloning of human Syk |
Law CL, Sidorenko SP, Chandran KA, Draves KE, Chan AC, Weiss A, Edelhoff S, Disteche CM, Clark EA |
A B cell protein-tyrosine kinase associated with the surface immunoglobulin M-B cell receptor complex J Biol Chem |
PMID 8163536 |
CD22 associates with the human surface IgM-B-cell antigen receptor complex |
Leprince C, Draves KE, Geahlen RL, Ledbetter JA, Clark EA |
Proc Natl Acad Sci U S A 1993 Apr 15;90(8):3236-40 |
PMID 8475064 |
Syk-dependent mTOR activation in follicular lymphoma cells |
Leseux L, Hamdi SM, Al Saati T, Capilla F, Recher C, Laurent G, Bezombes C |
Blood 2006 Dec 15;108(13):4156-62 |
PMID 16912221 |
Visualization of Syk-antigen receptor interactions using green fluorescent protein: differential roles for Syk and Lyn in the regulation of receptor capping and internalization |
Ma H, Yankee TM, Hu J, Asai DJ, Harrison ML, Geahlen RL |
J Immunol 2001 Feb 1;166(3):1507-16 |
PMID 11160190 |
Syk inhibitors as treatment for allergic rhinitis |
Masuda ES, Schmitz J |
Pulm Pharmacol Ther 2008;21(3):461-7 |
PMID 17669674 |
Syk activation in dendritic cells is essential for airway hyperresponsiveness and inflammation |
Matsubara S, Koya T, Takeda K, Joetham A, Miyahara N, Pine P, Masuda ES, Swasey CH, Gelfand EW |
Am J Respir Cell Mol Biol 2006 Apr;34(4):426-33 |
PMID 16339999 |
The SYK tyrosine kinase: a crucial player in diverse biological functions |
Mócsai A, Ruland J, Tybulewicz VL |
Nat Rev Immunol 2010 Jun;10(6):387-402 |
PMID 20467426 |
Molecular cloning of the human homologue to the pig protein-tyrosine kinase syk |
Müller B, Cooper L, Terhorst C |
Immunogenetics 1994;39(5):359-62 |
PMID 8168854 |
Solution structure of the C-terminal SH2 domain of the human tyrosine kinase Syk complexed with a phosphotyrosine pentapeptide |
Narula SS, Yuan RW, Adams SE, Green OM, Green J, Philips TB, Zydowsky LD, Botfield MC, Hatada M, Laird ER, et al |
Structure 1995 Oct 15;3(10):1061-73 |
PMID 8590001 |
Inhibition of spleen tyrosine kinase in the treatment of rheumatoid arthritis |
Nijjar JS, Tindell A, McInnes IB, Siebert S |
Rheumatology (Oxford) 2013 Sep;52(9):1556-62 |
PMID 23861534 |
Identification of seven genes regulated by wild-type p53 in a colon cancer cell line carrying a well-controlled wild-type p53 expression system |
Okamura S, Ng CC, Koyama K, Takei Y, Arakawa H, Monden M, Nakamura Y |
Oncol Res 1999;11(6):281-5 |
PMID 10691030 |
Distinct roles for Syk and ZAP-70 during early thymocyte development |
Palacios EH, Weiss A |
J Exp Med 2007 Jul 9;204(7):1703-15 |
Spleen tyrosine kinase inhibition in the treatment of autoimmune, allergic and autoinflammatory diseases |
Pamuk ON, Tsokos GC |
Arthritis Res Ther 2010;12(6):222 |
PMID 21211067 |
Ubiquitination and degradation of Syk and ZAP-70 protein tyrosine kinases in human NK cells upon CD16 engagement |
Paolini R, Molfetta R, Piccoli M, Frati L, Santoni A |
Proc Natl Acad Sci U S A 2001 Aug 14;98(17):9611-6 |
PMID 11493682 |
Therapeutic potential of spleen tyrosine kinase inhibition for treating high-risk precursor B cell acute lymphoblastic leukemia |
Perova T, Grandal I, Nutter LM, Papp E, Matei IR, Beyene J, Kowalski PE, Hitzler JK, Minden MD, Guidos CJ, Danska JS |
Sci Transl Med 2014 May 14;6(236):236ra62 |
PMID 24828076 |
Novel insights into the mechanism of decreased expression of type X collagen in human mesenchymal stem cells from patients with osteoarthritis cultured on nitrogen-rich plasma polymers: implication of cyclooxygenase-1 |
Petit A, Wang HT, Girard-Lauriault PL, Wertheimer MR, Antoniou J, Mwale F |
J Biomed Mater Res A 2010 Sep 1;94(3):744-50 |
PMID 20225218 |
Alternative splicing of SYK regulates mitosis and cell survival |
Prinos P, Garneau D, Lucier JF, Gendron D, Couture S, Boivin M, Brosseau JP, Lapointe E, Thibault P, Durand M, Tremblay K, Gervais-Bird J, Nwilati H, Klinck R, Chabot B, Perreault JP, Wellinger RJ, Elela SA |
Nat Struct Mol Biol 2011 Jun;18(6):673-9 |
PMID 21552259 |
Genomic and expression profiling identifies the B-cell associated tyrosine kinase Syk as a possible therapeutic target in mantle cell lymphoma |
Rinaldi A, Kwee I, Taborelli M, Largo C, Uccella S, Martin V, Poretti G, Gaidano G, Calabrese G, Martinelli G, Baldini L, Pruneri G, Capella C, Zucca E, Cotter FE, Cigudosa JC, Catapano CV, Tibiletti MG, Bertoni F |
Br J Haematol 2006 Feb;132(3):303-16 |
PMID 16409295 |
Splenic marginal zone lymphoma: proposal of new diagnostic and prognostic markers identified after tissue and cDNA microarray analysis |
Ruiz-Ballesteros E, Mollejo M, Rodriguez A, Camacho FI, Algara P, Martinez N, Pollán M, Sanchez-Aguilera A, Menarguez J, Campo E, Martinez P, Mateo M, Piris MA |
Blood 2005 Sep 1;106(5):1831-8 |
PMID 15914563 |
Structure and function of Syk protein-tyrosine kinase |
Sada K, Takano T, Yanagi S, Yamamura H |
J Biochem 2001 Aug;130(2):177-86 |
Syk: a new player in the field of breast cancer |
Stewart ZA, Pietenpol JA |
Breast Cancer Res 2001;3(1):5-7 |
PMID 11250739 |
Novel t(5;9)(q33;q22) fuses ITK to SYK in unspecified peripheral T-cell lymphoma |
Streubel B, Vinatzer U, Willheim M, Raderer M, Chott A |
Leukemia 2006 Feb;20(2):313-8 |
PMID 16341044 |
Molecular cloning of a porcine gene syk that encodes a 72-kDa protein-tyrosine kinase showing high susceptibility to proteolysis |
Taniguchi T, Kobayashi T, Kondo J, Takahashi K, Nakamura H, Suzuki J, Nagai K, Yamada T, Nakamura S, Yamamura H |
J Biol Chem 1991 Aug 25;266(24):15790-6 |
PMID 1874735 |
Complement-mediated phagocytosis--the role of Syk |
Tohyama Y, Yamamura H |
IUBMB Life 2006 May-Jun;58(5-6):304-8 |
PMID 16754322 |
Specific immunoglobulin E responses in ZAP-70-deficient patients are mediated by Syk-dependent T-cell receptor signalling |
Toyabe S, Watanabe A, Harada W, Karasawa T, Uchiyama M |
Immunology 2001 Jun;103(2):164-71 |
PMID 11412303 |
Molecular mechanism of the Syk activation switch |
Tsang E, Giannetti AM, Shaw D, Dinh M, Tse JK, Gandhi S, Ho H, Wang S, Papp E, Bradshaw JM |
J Biol Chem 2008 Nov 21;283(47):32650-9 |
PMID 18818202 |
Purification of a 72-kDa protein-tyrosine kinase from rat liver and its identification as Syk: involvement of Syk in signaling events of hepatocytes |
Tsuchida S, Yanagi S, Inatome R, Ding J, Hermann P, Tsujimura T, Matsui N, Yamamura H |
J Biochem 2000 Feb;127(2):321-7 |
PMID 10731700 |
Perinatal lethality and blocked B-cell development in mice lacking the tyrosine kinase Syk |
Turner M, Mee PJ, Costello PS, Williams O, Price AA, Duddy LP, Furlong MT, Geahlen RL, Tybulewicz VL |
Nature 1995 Nov 16;378(6554):298-302 |
PMID 7477352 |
Tyrosine kinase SYK: essential functions for immunoreceptor signalling |
Turner M, Schweighoffer E, Colucci F, Di Santo JP, Tybulewicz VL |
Immunol Today 2000 Mar;21(3):148-54 |
PMID 10689303 |
Alternative splicing disrupts a nuclear localization signal in spleen tyrosine kinase that is required for invasion suppression in breast cancer |
Wang L, Duke L, Zhang PS, Arlinghaus RB, Symmans WF, Sahin A, Mendez R, Dai JL |
Cancer Res 2003 Aug 1;63(15):4724-30 |
PMID 12907655 |
Hypermethylation of Syk gene in promoter region associated with oncogenesis and metastasis of gastric carcinoma |
Wang S, Ding YB, Chen GY, Xia JG, Wu ZY |
World J Gastroenterol 2004 Jun 15;10(12):1815-8 |
PMID 15188513 |
Targeting Syk as a treatment for allergic and autoimmune disorders |
Wong BR, Grossbard EB, Payan DG, Masuda ES |
Expert Opin Investig Drugs 2004 Jul;13(7):743-62 |
PMID 15212616 |
Association with B-cell-antigen receptor with protein-tyrosine kinase p72syk and activation by engagement of membrane IgM |
Yamada T, Taniguchi T, Yang C, Yasue S, Saito H, Yamamura H |
Eur J Biochem 1993 Apr 1;213(1):455-9 |
Syk expression and novel function in a wide variety of tissues |
Yanagi S, Inatome R, Takano T, Yamamura H |
Biochem Biophys Res Commun 2001 Nov 2;288(3):495-8 |
PMID 11676469 |
Hypermethylation leads to silencing of the SYK gene in human breast cancer |
Yuan Y, Mendez R, Sahin A, Dai JL |
Cancer Res 2001 Jul 15;61(14):5558-61 |
PMID 11454707 |
Phosphorylation of Syk activation loop tyrosines is essential for Syk function |
Zhang J, Billingsley ML, Kincaid RL, Siraganian RP |
An in vivo study using a specific anti-Syk activation loop phosphotyrosine antibody J Biol Chem |
PMID 10931839 |
Nucleocytoplasmic trafficking of the Syk protein tyrosine kinase |
Zhou F, Hu J, Ma H, Harrison ML, Geahlen RL |
Mol Cell Biol 2006 May;26(9):3478-91 |
PMID 16611990 |
Citation |
This paper should be referenced as such : |
Barnabas Nyesiga, Wingren, Anette Grloff |
SYK (spleen tyrosine kinase) |
Atlas Genet Cytogenet Oncol Haematol. 2016;20(11):545-551. |
Free journal version : [ pdf ] [ DOI ] |
History of this paper: |
Huret, JL. SYK (spleen tyrosine kinase). Atlas Genet Cytogenet Oncol Haematol. 2002;6(2):124-124. |
http://documents.irevues.inist.fr/bitstream/handle/2042/37844/02-2002-SYKID394.pdf |
Other Leukemias implicated (Data extracted from papers in the Atlas) [ 2 ] |
t(5;9)(q33;q22) ITK/SYK
t(9;12)(q22;p13) ETV6/SYK |
External links |
REVIEW articles | automatic search in PubMed |
Last year publications | automatic search in PubMed |
© Atlas of Genetics and Cytogenetics in Oncology and Haematology | indexed on : Fri Feb 19 18:01:09 CET 2021 |
For comments and suggestions or contributions, please contact us