Identifiers
HGNC:4566
HUGO:GRB2
growth factor receptor bound protein 2
HUGO:GRB2 hgnc_id:HGNC:4566 HGNC:4566 ENTREZ:2885 UNIPROT:P62993
HUGO:GRB2, HGNC:4566, ENTREZ:2885, UNIPROT:P62993, GENECARDS:GC17M073313
HUGO:GRB2 HGNC:4566 ENTREZ:2885 UNIPROT:P62993
HUGO:GRB2 HGNC:4566 ENTREZ:2885 UNIPROT:P62993 GENECARDS:GRB2 REACTOME:404631 KEGG:2885 ATLASONC:GRB2ID386ch17q25 WIKI:GRB2
Maps_Modules
HMC:AVOIDING_IMMUNE_DESTRUCTION
Adaptive Immune Response / TCR_SIGNALING
HMC:TUMOR_PROMOTING_INFLAMMATION
HMC:ACTIVATING_INVASION_AND_METASTASIS
Cancer Associated Fibroblasts / CORE
EMT Senescence / EMT_REGULATORS
Innate Immunity / IMMUNOSTIMULATORY_CORE_PATHWAYS
HMC:EVADING_GROWTH_SUPPRESSORS
Survival / MAPK
Survival / PI3K_AKT_MTOR
References
PMID:19449109
PMID:10811803 PMID:12640133 PMID:26552706
CASCADE:FGF
CASCADE:EGFR
GASCADE:IGF1R
PMID:15567848
Canonicaly growth factor pathways activates ERK sigvaling via GRB2/SOS/RAS/RAF/MAPK pathway, probably in fibroblast too.
PMID:11447289
Grb2 forms a complex with tyrosine-phosphorylated Shc in FGF-stimulated fibroblasts in an FRS2??-independent manner
PMID:10567412; PMID:15567848
EGFR activates ERK via GRB2/SOS/RAS/RAF pathway
EGFR induces SHC phosphorylation, directly interacts with GRB2 and induces formation of SHC:GRB2:SOS activated complex.
PMID:12175651; PMID:10086337
Upon IGF-IR autophosphorylation the protein Shc is recruited to the receptor and becomes phosphorylated on tyrosine residues.36 Activated Shc then binds the adaptor Grb2 in an IRS-1-independent manner, leading to activation of the Ras-ERK pathway.36 This pathway of IGF-IR signaling has been most closely associated with cell differentiation and migration, but in some cases also can regulate the machinery of apoptosis, for example, in detachment-induced death, or anoikis, in fibroblasts.
PMID:17673906
SHC1 gene has 3 corresponding protein isoforms: p66, p52 and p46
Upon TGFB stimulation, the activated TGFBR1 recruits and directly phosphorylates SHC1 (p66 or p52) on tyrosine and serine.
TGFB-induced SHC1 phosphorylation induces SHC1 (p66 or p52) association with Grb2 and Sos
GRB2 is an adaptator for Ras
MACROPHAGE
NATURAL_KILLER
CASCADE:NKG2D
CASCADE:IL4
CASCADE:Fc_gamma_RIII
CASCADE:INTEGRIN_A4B1
CASCADE:INTEGRIN_A5B1
PMID:16887996, PMID:16582911??
Vav1 interacts with DAP10 YxNM motifs through the adaptor protein Grb2 and is required for activation of PI3K-dependent Akt signaling.
binding of DAP10??? ???to either p85??? ???or Grb2??? ???alone is not sufficient to trigger DAP10-mediated cytotoxicity and that both binding sites are necessary for NKG2D-initiated killing.
PMID:10982827
Shc and GRB2 mediate Gab2 tyrosyl phosphorylation. Mutation of the three tyrosyl phosphorylation sites of Shc, which bind Grb2, blocks the ability of the Shc chimera to evoke Gab2 tyrosyl phosphorylation in B cells
PMID:8551221
SHC1 protein is phosphorylated upon CD16 and IL-2R Stimulation in Human NK Cells and interacts with GRB2
Grb2 is an adaptor protein normally present in cytosol. It is recruited to the plasma membrane by activated RTK.
PMID:17496910
PMID:15574420
PMID:11777939
→ GRB2@INNATE_IMMUNE_CELL_Cytosol
+ DAP10:NKG2D*@INNATE_IMMUNE_CELL_Membrane → DAP10|pho:GRB2:NKG2D*@INNATE_IMMUNE_CELL_Membrane
+ GRB2@INNATE_IMMUNE_CELL_Cytosol → GRB2:LAT|pho@INNATE_IMMUNE_CELL_Cytosol
+ SHC1|pho@INNATE_IMMUNE_CELL_Cytosol → GRB2:SHC1|pho@INNATE_IMMUNE_CELL_Cytosol
→ PI3KR(p85)*@INNATE_IMMUNE_CELL_Cytosol
→ VAV1|pho|active@INNATE_IMMUNE_CELL_Cytosol
→ LCP2|pho@INNATE_IMMUNE_CELL_Cytosol
→ PLCG2|pho@INNATE_IMMUNE_CELL_Cytosol
→ PLCG1|pho@INNATE_IMMUNE_CELL_Cytosol
→ CBL|pho|active@INNATE_IMMUNE_CELL_Cytosol
→ GAB2|pho@INNATE_IMMUNE_CELL_Cytosol
+ CD11a*@INNATE_IMMUNE_CELL_Membrane → CD11a*:CD18*@INNATE_IMMUNE_CELL_Membrane
+ ITGA4@INNATE_IMMUNE_CELL_Membrane → (ITGA4:ITGB1)|active@INNATE_IMMUNE_CELL_Membrane
→ SOS*@INNATE_IMMUNE_CELL_Cytosol