GRB2 (Growth factor receptor-bound protein 2)

2007-05-01   Gagani Athauda , Donald P Bottaro 





The GRB2 gene structure consists of five exons (ranging from 78 to 186 bp) and four introns (from approximately 1 to approximately 7 kb). Two human mRNA transcript variants arise from alternative splicing. GRB2 variant 1 mRNA encodes protein isoform 1, which is longer. Variant 2 mRNA, which encodes protein isoform 2, lacks an in-frame exon present in the 3 coding region of variant 1 encompassing residues 59 - 100 of the mature protein (see Protein, below).


At least one potential human pseudogene may exist: LOC391157. A pseudogene of the mouse Grb2 homolog, known as Grb2-ps1 (growth factor receptor bound protein 2, pseudogene 1) also has been identified.


Atlas Image
A schematic representation of the domain structure of GRB2, which consists of a single Src homology 2 (SH2) domain (residues 59 - 152) flanked by two SH3 domains (amino-terminal: residues 3 - 54; carboxy-terminal: residues 160-212).


GRB2 (isoform 1) is a 217 residue protein with an expected molecular mass of 25,206 Da. GRB2 protein has homology to non-catalytic regions of c-Src, consisting of a single Src homology 2 (SH2) domain flanked by two Src homology 3 (SH3) domains. GRB2 isoform 2, encoded by an alternatively spliced mRNA transcript known as variant 2, has a deletion in the amino-terminal portion of the SH2 domain encompassing residues 59 - 100 of isoform 1. This protein isoform, known originally as GRB3-3, does not bind to phosphotyrosyl-containing proteins like isoform 1, but retains two functional SH3 domains.


Expressed in virtually all embryonic and adult tissues.


Primarily cytosolic, but transient plasma membrane and nuclear localizations have been reported.


Cell surface receptor signaling - The two GRB2 SH3 domains bind to the proline-rich regions of the guanine nucleotide releasing factor son of sevenless (SOS-1) protein, and the GRB2-SOS-1 complex preexists in the cytoplasm of resting cells. Phosphotyrosyl residues on in the context of the motif NH2- pYXNX-COOH (where pY represents phosphotyrosine, N represents asparagine, and X represents any other residue) are selectively recognized by the GRB2 SH2 domain. Growth factor receptor tyrosine kinases (RTKs), including those for epidermal growth factor (EGF), fibroblast growth factor, nerve growth factor (TrkA/TrkB), platelet-derived growth factor, colony-stimulating factor-1, and hepatocyte growth factor (HGF), as well as non-receptor tyrosine kinases (TKs) such as BCR-Abl and focal adhesion kinase (FAK), intracellular effectors such as insulin receptor substrate-1 and Shc, and phosphotyrosine phosphatases such as SHP-2 (PTPN11) and receptor-like tyrosine phosphatase alpha, all conditionally possess the pYXNX motif. Note that the environmental cue leading to protein tyrosyl phosphorylation on an appropriate GRB2 recognition motif is independent of GRB2 interaction; thus, ligand independent EGFR activation, such as growth hormone-induced EGFR tyrosine phosphorylation by JAK2, also leads to GRB2-mediated ERK kinase pathway activation and c-fos expression. Similarly, mechanical stress leading to increased angiotensin II production and transactivation of EGFR and other intracellular kinases implicates GRB2 recruitment in cardiac hypertrophy and myocardial remodeling.
In many mitogenic signaling pathways, recruitment of GRB2 from the cytosol, where it is already bound to the guanine nucleotide exchange factor SOS-1 via its amino-terminal SH3 domain, brings SOS1 in close proximity to Ras at the plasma membrane. Ras, a small GTPase in the GDP-bound inactive state in quiescent cells, then undergoes nucleotide exchange of GDP for GTP, which facilitates binding of the serine/threonine protein kinase Raf-1 and its subsequent activation. This initiates a cascade of kinase activation: activated Raf-1 phosphorylates and activates MEK1/MEK2, which in turn phosphorylate and stimulate the MAP kinases ERK1/ERK2. Activated ERKs translocate to the nucleus and phosphorylate transcription factors such as Elk-1, STAT1, STAT3 and Myc, activating gene expression. In parallel, the phosphatidyl inositol 3-kinase (PI3K)/Akt pathway is activated via the adaptor Gab1, which is bound to the GRB2 carboxyl-terminal SH3 domain in many epithelial cell types. The gene expression programs activated by these pathways initiate a spectrum of fundamental cellular activities including proliferation, growth (increase in cell size), differentiation and survival. These processes are critical for normal embryonic development and adult homeostasis, and are frequently aberrantly activated in cancer.
Stimulation of the T cell antigen receptor (TCR) induces the tyrosine phosphorylation of a variety of cellular proteins, including a protein called p36-38 or Linker for Activation of T cells (LAT), a protein tightly associated with the plasma membrane. Tyrosyl-phosphorylated sequences of LAT bind to the GRB2 SH2 domain. In these cells the SH3 domains of GRB2 bind Vav-family proteins, guanine nucleotide exchange factors for Rho-family GTPases. These interactions are essential for TCR-induced calcium flux and activation of the MAP kinase cascade, ultimately leading to T cell proliferation and effector functions.
Receptor endocytosis and ubiquitinylation - Upon ligand-dependant activation of EGFR TK, c-Cbl binds to the EGFR directly through its SH2 domain and indirectly through its SH3 domain. c-Cbl binding and its consequential phosphorylation results in activation of the E3 ubiquitin ligase complex of which c-Cbl is a component, resulting in receptor ubiquitinylation. GRB2 also regulates internalization of EGF receptors through clathrin-coated pits.
Actin-based cell motility - GRB2 participates directly in the regulation of actin filament formation and actin-based cell motility. GRB2 is a critical link between Wiskott-Aldrich Syndrome protein (WASp) and the actin cytoskeleton; WAS patients show defects in T cell polarization and migration in response to physiologic stimuli, resulting in thrombocytopenia, eczema and immunodeficiency. Studies of WASp function and the intracellular motility of invasive microbial pathogens such as Listeria monocytogenes and Vaccinia virus helped to elucidate an important role for GRB2 in directly promoting actin based motility. In most mammalian cells, the WASp family member N-WASp interacts with the Arp2/3 complex and G-actin to stimulate actin polymerization. N-WASp activity is enhanced by other effectors such as Nck, Cdc42 and GRB2; disruption of GRB2 SH3 or SH2 domains diminishes actin polymerization and thus actin-based motility.


GRB2 amino acid sequence is very highly conserved among species. Human GRB2 shows 50% overall amino acid sequence identity with S. cerevisiae YPR154w, 58% identity with Sem-5 of C. elegans, 66% identity with the D. melanogaster homolog Drk and over 99% identity with both rat and mouse homologs.



No known naturally-occurring mutations in human GRB2 have been reported.

Implicated in

Entity name
Normal embryogenesis
A null mutation introduced into the mouse gene for Grb2 was used to demonstrate that Grb2 is required during embryogenesis for the differentiation of endodermal cells and epiblast formation. Replacing the carboxy-terminus of SOS-1 with the Grb2 SH2 domain yielded a fusion protein that rescued the defects caused by this Grb2 mutation. Grb2 signaling primarily regulates differentiation, rather than proliferation, in the early mouse embryo.
Entity name
Cardiac hypertrophy
Engineered Grb2 +/- mice subjected to cardiac stress failed to activate p38 MAP kinase (MAPK14) and Jun N-terminal kinase (JNK), and the cardiac hypertrophy and fibrosis observed in normal mice were blocked. Transgenic mice with dominant-negative forms of MAPK p38-alpha and p38-beta developed cardiac hypertrophy but were resistant to cardiac fibrosis when subjected to cardiac stress. These and other findings suggest that Grb2 activity is essential for cardiac hypertrophy and fibrosis in response to pressure overload, and that different signaling pathways downstream of Grb2 regulate fibrosis, fetal gene induction, and cardiomyocyte growth.
Entity name
As a pivotal activator of cell-cycle control and motility pathways downstream of several growth factor receptors, GRB2 is involved in oncogenic signaling in a wide variety of human tumors. For example, GRB2 directly interacts with SOS-1 and the Bcr portion of the Bcr-Abl fusion protein, a tyrosine kinase oncoprotein which has been implicated in the pathogenesis of Philadelphia chromosome positive leukemias, such as CML, ALL, and AML. GRB2 is rate limiting for mammary carcinomas induced by polyomavirus middle T antigen. GRB2 over expression has been reported in human breast, bladder and prostate cancer cell lines. Selective small molecule inhibitors of GRB2 SH2 domain binding block solid tumor metastasis in animal models.


Pubmed IDLast YearTitleAuthors
100221191999Concomitant activation of pathways downstream of Grb2 and PI 3-kinase is required for MET-mediated metastasis.Bardelli A et al
146851702003Met, metastasis, motility and more.Birchmeier C et al
100514061999The gene structure of the human growth factor bound protein GRB2.Bochmann H et al
126556412003Actin-based motility: from molecules to movement.Carlier MF et al
98656971998Mammalian Grb2 regulates multiple steps in embryonic development and malignant transformation.Cheng AM et al
13723951992C. elegans cell-signalling gene sem-5 encodes a protein with SH2 and SH3 domains.Clark SG et al
163172852006Molecular targeting of growth factor receptor-bound 2 (Grb2) as an anti-cancer strategy.Dharmawardana PG et al
86627331996Pathways downstream of Shc and Grb2 are required for cell transformation by the tpr-Met oncoprotein.Fixman ED et al
93911191997A point mutation in the MET oncogene abrogates metastasis without affecting transformation.Giordano S et al
74799041995Mutant forms of growth factor-binding protein-2 reverse BCR-ABL-induced transformation.Gishizky ML et al
176166552007Inhibition of tumor metastasis by a growth factor receptor bound protein 2 Src homology 2 domain-binding antagonist.Giubellino A et al
111355752001Disruption of T cell signaling networks and development by Grb2 haploid insufficiency.Gong Q et al
79707201994Activation of the Ras signalling pathway in human breast cancer cells overexpressing erbB-2.Janes PW et al
120066502002Coordinated traffic of Grb2 and Ras during epidermal growth factor receptor endocytosis visualized in living cells.Jiang X et al
13227981992The SH2 and SH3 domain-containing protein GRB2 links receptor tyrosine kinases to ras signaling.Lowenstein EJ et al
147093372004Potentiation of signal transduction mitogenesis and cellular proliferation upon binding of receptor-recognized forms of alpha2-macroglobulin to 1-LN prostate cancer cells.Misra UK et al
84620981993A Drosophila SH2-SH3 adaptor protein implicated in coupling the sevenless tyrosine kinase to an activator of Ras guanine nucleotide exchange, Sos.Olivier JP et al
84028961993BCR-ABL-induced oncogenesis is mediated by direct interaction with the SH2 domain of the GRB-2 adaptor protein.Pendergast AM et al
86628891996Specific uncoupling of GRB2 from the Met receptor. Differential effects on transformation and motility.Ponzetto C et al
118966122002Use of signal specific receptor tyrosine kinase oncoproteins reveals that pathways downstream from Grb2 or Shc are sufficient for cell transformation and metastasis.Saucier C et al
120074182002Grb2 and Nck act cooperatively to promote actin-based motility of vaccinia virus.Scaplehorn N et al
84620971993An SH3-SH2-SH3 protein is required for p21Ras1 activation and binds to sevenless and Sos proteins in vitro.Simon MA et al
83057381993The human GRB2 and Drosophila Drk genes can functionally replace the Caenorhabditis elegans cell signaling gene sem-5.Stern MJ et al
158861162005Vav-family proteins in T-cell signalling.Tybulewicz VL et al
109950352000Significance of the Grb2 and son of sevenless (Sos) proteins in human bladder cancer cell lines.Watanabe T et al
97902261998Growth hormone-induced tyrosine phosphorylation of EGF receptor as an essential element leading to MAP kinase activation and gene expression.Yamauchi T et al
110546642000Up-regulation of the protein tyrosine phosphatase SHP-1 in human breast cancer and correlation with GRB2 expression.Yip SS et al
105313811999Ligand-induced ubiquitination of the epidermal growth factor receptor involves the interaction of the c-Cbl RING finger and UbcH7.Yokouchi M et al
156728682004KGF-induced motility of breast cancer cells is dependent on Grb2 and Erk1,2.Zang XP et al
126399892003The role of the Grb2-p38 MAPK signaling pathway in cardiac hypertrophy and fibrosis.Zhang S et al
107237962000The role of membrane-associated adaptors in T cell receptor signalling.Zhang W et al

Other Information

Locus ID:

NCBI: 2885
MIM: 108355
HGNC: 4566
Ensembl: ENSG00000177885


dbSNP: 2885
ClinVar: 2885
TCGA: ENSG00000177885


Gene IDTranscript IDUniprot

Expression (GTEx)



PathwaySourceExternal ID
MAPK signaling pathwayKEGGko04010
ErbB signaling pathwayKEGGko04012
mTOR signaling pathwayKEGGko04150
Dorso-ventral axis formationKEGGko04320
Focal adhesionKEGGko04510
Gap junctionKEGGko04540
Jak-STAT signaling pathwayKEGGko04630
Natural killer cell mediated cytotoxicityKEGGko04650
T cell receptor signaling pathwayKEGGko04660
B cell receptor signaling pathwayKEGGko04662
Fc epsilon RI signaling pathwayKEGGko04664
Insulin signaling pathwayKEGGko04910
GnRH signaling pathwayKEGGko04912
Renal cell carcinomaKEGGko05211
Endometrial cancerKEGGko05213
Prostate cancerKEGGko05215
Chronic myeloid leukemiaKEGGko05220
Acute myeloid leukemiaKEGGko05221
Non-small cell lung cancerKEGGko05223
MAPK signaling pathwayKEGGhsa04010
ErbB signaling pathwayKEGGhsa04012
mTOR signaling pathwayKEGGhsa04150
Focal adhesionKEGGhsa04510
Gap junctionKEGGhsa04540
Jak-STAT signaling pathwayKEGGhsa04630
Natural killer cell mediated cytotoxicityKEGGhsa04650
T cell receptor signaling pathwayKEGGhsa04660
B cell receptor signaling pathwayKEGGhsa04662
Fc epsilon RI signaling pathwayKEGGhsa04664
Insulin signaling pathwayKEGGhsa04910
GnRH signaling pathwayKEGGhsa04912
Pathways in cancerKEGGhsa05200
Renal cell carcinomaKEGGhsa05211
Endometrial cancerKEGGhsa05213
Prostate cancerKEGGhsa05215
Chronic myeloid leukemiaKEGGhsa05220
Acute myeloid leukemiaKEGGhsa05221
Non-small cell lung cancerKEGGhsa05223
Chemokine signaling pathwayKEGGko04062
Chemokine signaling pathwayKEGGhsa04062
Neurotrophin signaling pathwayKEGGko04722
Neurotrophin signaling pathwayKEGGhsa04722
Dorso-ventral axis formationKEGGhsa04320
Hepatitis CKEGGko05160
Hepatitis CKEGGhsa05160
Osteoclast differentiationKEGGko04380
Osteoclast differentiationKEGGhsa04380
Viral carcinogenesisKEGGhsa05203
Viral carcinogenesisKEGGko05203
PI3K-Akt signaling pathwayKEGGhsa04151
PI3K-Akt signaling pathwayKEGGko04151
Hepatitis BKEGGhsa05161
Proteoglycans in cancerKEGGhsa05205
Proteoglycans in cancerKEGGko05205
Estrogen signaling pathwayKEGGhsa04915
Estrogen signaling pathwayKEGGko04915
Prolactin signaling pathwayKEGGhsa04917
Prolactin signaling pathwayKEGGko04917
MicroRNAs in cancerKEGGhsa05206
MicroRNAs in cancerKEGGko05206
Ras signaling pathwayKEGGhsa04014
FoxO signaling pathwayKEGGhsa04068
Signaling pathways regulating pluripotency of stem cellsKEGGhsa04550
Signaling pathways regulating pluripotency of stem cellsKEGGko04550
Choline metabolism in cancerKEGGhsa05231
Choline metabolism in cancerKEGGko05231
Diseases of signal transductionREACTOMER-HSA-5663202
Signaling by EGFR in CancerREACTOMER-HSA-1643713
Signaling by Ligand-Responsive EGFR Variants in CancerREACTOMER-HSA-5637815
Constitutive Signaling by Ligand-Responsive EGFR Cancer VariantsREACTOMER-HSA-1236382
Signaling by EGFRvIII in CancerREACTOMER-HSA-5637812
Constitutive Signaling by EGFRvIIIREACTOMER-HSA-5637810
Signaling by FGFR in diseaseREACTOMER-HSA-1226099
Signaling by FGFR1 in diseaseREACTOMER-HSA-5655302
FGFR1 mutant receptor activationREACTOMER-HSA-1839124
Signaling by cytosolic FGFR1 fusion mutantsREACTOMER-HSA-1839117
Signaling by FGFR2 in diseaseREACTOMER-HSA-5655253
Signaling by FGFR3 in diseaseREACTOMER-HSA-5655332
Signaling by FGFR4 in diseaseREACTOMER-HSA-5655291
PI3K/AKT Signaling in CancerREACTOMER-HSA-2219528
Constitutive Signaling by Aberrant PI3K in CancerREACTOMER-HSA-2219530
Infectious diseaseREACTOMER-HSA-5663205
Immune SystemREACTOMER-HSA-168256
Adaptive Immune SystemREACTOMER-HSA-1280218
Costimulation by the CD28 familyREACTOMER-HSA-388841
CD28 co-stimulationREACTOMER-HSA-389356
CD28 dependent Vav1 pathwayREACTOMER-HSA-389359
Signaling by the B Cell Receptor (BCR)REACTOMER-HSA-983705
Antigen activates B Cell Receptor (BCR) leading to generation of second messengersREACTOMER-HSA-983695
Downstream signaling events of B Cell Receptor (BCR)REACTOMER-HSA-1168372
PIP3 activates AKT signalingREACTOMER-HSA-1257604
Negative regulation of the PI3K/AKT networkREACTOMER-HSA-199418
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
FCERI mediated Ca+2 mobilizationREACTOMER-HSA-2871809
Role of LAT2/NTAL/LAB on calcium mobilizationREACTOMER-HSA-2730905
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
Regulation of signaling by CBLREACTOMER-HSA-912631
Platelet activation, signaling and aggregationREACTOMER-HSA-76002
GPVI-mediated activation cascadeREACTOMER-HSA-114604
Platelet Aggregation (Plug Formation)REACTOMER-HSA-76009
Integrin alphaIIb beta3 signalingREACTOMER-HSA-354192
GRB2:SOS provides linkage to MAPK signaling for IntegrinsREACTOMER-HSA-354194
Cell surface interactions at the vascular wallREACTOMER-HSA-202733
Tie2 SignalingREACTOMER-HSA-210993
Signal TransductionREACTOMER-HSA-162582
Signaling by EGFRREACTOMER-HSA-177929
GRB2 events in EGFR signalingREACTOMER-HSA-179812
SHC1 events in EGFR signalingREACTOMER-HSA-180336
GAB1 signalosomeREACTOMER-HSA-180292
EGFR downregulationREACTOMER-HSA-182971
Signaling by FGFRREACTOMER-HSA-190236
Signaling by FGFR1REACTOMER-HSA-5654736
Downstream signaling of activated FGFR1REACTOMER-HSA-5654687
FRS-mediated FGFR1 signalingREACTOMER-HSA-5654693
SHC-mediated cascade:FGFR1REACTOMER-HSA-5654688
PI-3K cascade:FGFR1REACTOMER-HSA-5654689
Negative regulation of FGFR1 signalingREACTOMER-HSA-5654726
Spry regulation of FGF signalingREACTOMER-HSA-1295596
Signaling by FGFR2REACTOMER-HSA-5654738
Downstream signaling of activated FGFR2REACTOMER-HSA-5654696
FRS-mediated FGFR2 signalingREACTOMER-HSA-5654700
SHC-mediated cascade:FGFR2REACTOMER-HSA-5654699
PI-3K cascade:FGFR2REACTOMER-HSA-5654695
Negative regulation of FGFR2 signalingREACTOMER-HSA-5654727
Signaling by FGFR3REACTOMER-HSA-5654741
Downstream signaling of activated FGFR3REACTOMER-HSA-5654708
FRS-mediated FGFR3 signalingREACTOMER-HSA-5654706
SHC-mediated cascade:FGFR3REACTOMER-HSA-5654704
PI-3K cascade:FGFR3REACTOMER-HSA-5654710
Negative regulation of FGFR3 signalingREACTOMER-HSA-5654732
Signaling by FGFR4REACTOMER-HSA-5654743
Downstream signaling of activated FGFR4REACTOMER-HSA-5654716
FRS-mediated FGFR4 signalingREACTOMER-HSA-5654712
SHC-mediated cascade:FGFR4REACTOMER-HSA-5654719
PI-3K cascade:FGFR4REACTOMER-HSA-5654720
Negative regulation of FGFR4 signalingREACTOMER-HSA-5654733
Signaling by Insulin receptorREACTOMER-HSA-74752
Insulin receptor signalling cascadeREACTOMER-HSA-74751
IRS-mediated signallingREACTOMER-HSA-112399
PI3K CascadeREACTOMER-HSA-109704
SOS-mediated signallingREACTOMER-HSA-112412
Signal attenuationREACTOMER-HSA-74749
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
PI3K/AKT activationREACTOMER-HSA-198203
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
Regulation of KIT signalingREACTOMER-HSA-1433559
Signaling by ERBB2REACTOMER-HSA-1227986
SHC1 events in ERBB2 signalingREACTOMER-HSA-1250196
GRB2 events in ERBB2 signalingREACTOMER-HSA-1963640
PI3K events in ERBB2 signalingREACTOMER-HSA-1963642
Signaling by ERBB4REACTOMER-HSA-1236394
SHC1 events in ERBB4 signalingREACTOMER-HSA-1250347
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
GPCR downstream signalingREACTOMER-HSA-388396
G-protein beta:gamma signallingREACTOMER-HSA-397795
G beta:gamma signalling through PI3KgammaREACTOMER-HSA-392451
Gastrin-CREB signalling pathway via PKC and MAPKREACTOMER-HSA-881907
EGFR Transactivation by GastrinREACTOMER-HSA-2179392
Signaling by Type 1 Insulin-like Growth Factor 1 Receptor (IGF1R)REACTOMER-HSA-2404192
IGF1R signaling cascadeREACTOMER-HSA-2428924
SHC-related events triggered by IGF1RREACTOMER-HSA-2428933
IRS-related events triggered by IGF1RREACTOMER-HSA-2428928
Signaling by LeptinREACTOMER-HSA-2586552
Vesicle-mediated transportREACTOMER-HSA-5653656
Membrane TraffickingREACTOMER-HSA-199991
Cell-Cell communicationREACTOMER-HSA-1500931
Signal regulatory protein (SIRP) family interactionsREACTOMER-HSA-391160
Developmental BiologyREACTOMER-HSA-1266738
Axon guidanceREACTOMER-HSA-422475
NCAM signaling for neurite out-growthREACTOMER-HSA-375165
Phospholipase D signaling pathwayKEGGko04072
Phospholipase D signaling pathwayKEGGhsa04072
PI5P, PP2A and IER3 Regulate PI3K/AKT SignalingREACTOMER-HSA-6811558
Signaling by FGFR3 point mutants in cancerREACTOMER-HSA-8853338
Signaling by FGFR3 fusions in cancerREACTOMER-HSA-8853334
EGFR tyrosine kinase inhibitor resistanceKEGGko01521
Endocrine resistanceKEGGko01522
EGFR tyrosine kinase inhibitor resistanceKEGGhsa01521
Endocrine resistanceKEGGhsa01522
Clathrin-mediated endocytosisREACTOMER-HSA-8856828
Cargo recognition for clathrin-mediated endocytosisREACTOMER-HSA-8856825
RET signalingREACTOMER-HSA-8853659
Breast cancerKEGGko05224
Breast cancerKEGGhsa05224
Signaling by METREACTOMER-HSA-6806834
MET activates RAS signalingREACTOMER-HSA-8851805
MET activates PI3K/AKT signalingREACTOMER-HSA-8851907
MET activates PTPN11REACTOMER-HSA-8865999
MET promotes cell motilityREACTOMER-HSA-8875878
MET activates RAP1 and RAC1REACTOMER-HSA-8875555
MET receptor recyclingREACTOMER-HSA-8875656
Negative regulation of MET activityREACTOMER-HSA-6807004
Listeria monocytogenes entry into host cellsREACTOMER-HSA-8876384
InlB-mediated entry of Listeria monocytogenes into host cellREACTOMER-HSA-8875360

Protein levels (Protein atlas)

Not detected


Entity IDNameTypeEvidenceAssociationPKPDPMIDs


Pubmed IDYearTitleCitations
167290432005Phosphotyrosine interactome of the ErbB-receptor kinase family.193
169061592006Oligomerization of signaling complexes by the multipoint binding of GRB2 to both LAT and SOS1.89
199131212009Gene-centric association signals for lipids and apolipoproteins identified via the HumanCVD BeadChip.85
184673322008Phosphorylation regulates tau interactions with Src homology 3 domains of phosphatidylinositol 3-kinase, phospholipase Cgamma1, Grb2, and Src family kinases.77
217060162011Selected reaction monitoring mass spectrometry reveals the dynamics of signaling through the GRB2 adaptor.75
120066502002Coordinated traffic of Grb2 and Ras during epidermal growth factor receptor endocytosis visualized in living cells.62
203796142010Personalized smoking cessation: interactions between nicotine dose, dependence and quit-success genotype score.62
121869042002Subversion of cell signaling pathways by hepatitis C virus nonstructural 5A protein via interaction with Grb2 and P85 phosphatidylinositol 3-kinase.56
227264382012Inhibition of basal FGF receptor signaling by dimeric Grb2.56
120074182002Grb2 and Nck act cooperatively to promote actin-based motility of vaccinia virus.54


Gagani Athauda ; Donald P Bottaro

GRB2 (Growth factor receptor-bound protein 2)

Atlas Genet Cytogenet Oncol Haematol. 2007-05-01

Online version: