Growth factor triggering of protein tyrosine kinase receptors induces signals that cascade to the nucleus, activating mitogenic as well as other responses. Critical components of this process include adapter proteins such as Shc, IRS-1 and Gab 1 (GRB-associated binder-1) that lack detectable catalytic activity (1-3,8). Gab1 can be phosphorylated by multiple receptor tyrosine kinase (RTKs), including: insulin receptor (IR), platelet derived growth factor receptor beta] (PDGFRbeta]), hepatocyte growth factor/scatter factor receptor (HGFR/SFR or c Met), and epidermal growth factor receptor (EGF), as well as in response to cell cell adhesion. Gab1 is tyrosine phosphorylated on at least 16 sites, some of which serve as binding sites for phosphoatidylinositol 3 kinase (PI3K), Grb2, PLC gamma 1, Nck, and SHP2. Phosphorylation of Gab1 on tyrosines 627 and 659 is critical for its binding to SHP2, and for activation of the ERK/MAPK pathway in response to EGF.
Function:
Adapter protein that plays a role in intracellular signaling cascades triggered by activated receptor-type kinases. Plays a role in FGFR1 signaling. Probably involved in signaling by the epidermal growth factor receptor (EGFR) and the insulin receptor (INSR).
Subunit:
Phosphorylated in response to FGFR1 activation. Phosphorylated on tyrosine residue(s) by the epidermal growth factor receptor (EGFR) and the insulin receptor (INSR). Tyrosine phosphorylation of GAB1 mediates interaction with several proteins that contain SH2 domains.
Similarity:
Belongs to the GAB family.
Contains 1 PH domain.
SWISS:
Q1396
Gene ID:
2549
Database links:
Entrez Gene: 2549 Human
Entrez Gene: 14388 Mouse
Entrez Gene: 361388 Rat
SwissProt: Q1396 Human
SwissProt: Q9QYY0 Mouse
Gab1作为一种分布广泛的接头蛋白，几乎能连接所有类型的受体（如酪氨酸激酶受体、G-蛋白偶联受体、细胞因子与抗原受体等，Gab1蛋白属于接头蛋白Gab家族,该家族蛋白因能与生长因子受体结合蛋白2（Grb2）相结合而得名。作为接头蛋白,Gab1蛋白能被多种受体酪氨酸激酶或非受体酪氨酸激酶激活,接受胞外多种生长因子、细胞因子和一些T/B细胞抗原受体的刺激,介导PI3K/Akt和Ras/MAPK等多条信号转导途径,具有促进细胞生长、迁移、调节免疫等多种生物学功能,与糖尿病、肿瘤、心血管疾病等的发生发展密切相关。
|
|
