GRB2-associated-binding protein 1 (GAB1)

GRB2-associated-binding protein 1 (GAB1) is an intracellular **adapter/docking protein** that plays a pivotal role in transmitting and diversifying signals from activated cell surface receptors, especially receptor tyrosine kinases such as the hepatocyte growth factor receptor (MET), epidermal growth factor receptor (EGFR), platelet-derived growth factor receptor (PDGFR), and fibroblast growth factor receptor 1 (FGFR1)[4][5][6]. GAB1 lacks enzymatic activity but undergoes **tyrosine phosphorylation** in response to growth factor stimulation, providing binding sites for multiple effectors, including PI3K (through its p85 subunit), phospholipase C-gamma1, SHP2 phosphatase, CRK, and ERK1/2[4][5][6]. This positions GAB1 as a central integrator and amplifier of complex signaling cascades that control cell growth, proliferation, survival, migration, morphogenesis, and branching tubulogenesis[2][4][6]. Dysregulation of GAB1-mediated signaling has been implicated in cancer, inflammation, fibrosis, and certain hereditary disorders such as DFNB26-related deafness[2][3][6]. GAB1 functions downstream of, and in cooperation with, adapter proteins like GRB2, and contains domains (pleckstrin homology, multiple tyrosine motifs) that recruit and organize multi-protein complexes at activated plasma membrane receptors[4][5][6].

Other names

Gab1Grb2-associated binder 1Growth factor receptor bound protein 2-associated protein 1Deafness, autosomal recessive 26 (DFNB26)

Not directly targeted by approved drugs; acts as a signal integration hub, so inhibitors of upstream receptors (e.g., MET, EGFR) or downstream signaling (e.g., PI3K, MAPK inhibitors) indirectly affect its pathway[4][5][6].