Grb2 is best known for its ability to link the epidermal growth factor receptor tyrosine kinase to the activation of Ras and its downstream kinases, ERK1,2. Grb2 is composed of an SH2 domain flanked on each side by an SH3 domain.

GRB2, in turn, binds to the Son of Sevenless (SOS) protein through its SH3 domain. This binding facilitates the activation of Ras, a small GTPase, which triggers a cascade of downstream signaling events, ultimately leading to cell proliferation, survival, and differentiation.

Sep 28, 2022 · Grb2 binds to Sos and to activated RTKs at the cell surface bringing Sos into close proximity of its substrate RAS. Sos activates downstream signalling via RAS.

RAS activation is a multiple‐step process in which linkage of the extracellular stimuli to the RAS activator SOS1 is the main step in RAS activation. GRB2 adaptor protein is the main modulator in SOS1 recruitment to the plasma membrane and its activation.

Grb2 is constitutively associated with Ras guanine-nucleotide exchange factor mSOS1/2 via its SH3 domains, whereas the Grb2 SH2 domain mediates binding to EGFR phosphotyrosines Tyr1068 and Tyr1086 (Li et al., 1993; Rozakis-Adcock …

Sep 30, 2022 · Ras activation is a crucial driver of cancer pathogenesis but efforts to target it have largely failed. Activation is mediated by formation of the Grb2-Sos complex. We find that Grb2 isoform Grb3-3 diminishes Ras activation due to competition for Sos binding, and is reduced in tumour tissue.

Jun 25, 1993 · Insulin activates Ras primarily by increasing the rate of guanine nucleotide-releasing activity. Here, we show that insulin-induced activation of ERKs was enhanced by stable overexpression of growth factor receptor-bound protein 2 (GRB2) but not by overexpression of GRB2 proteins with point mutations in the Src homology 2 and 3 domains.

Sep 1, 2024 · This review centers on GRB2, also known as Growth Factor Receptor-Bound Protein 2, a crucial adaptor protein integral to fundamental cellular pathways, with a specific emphasis on unraveling the internal dynamics that dictate its functionality.

Nov 6, 2012 · Grb2, initially discovered as the missing link between the epidermal growth factor receptor (EGFR) and the Ras–mitogen-activated protein kinase (MAPK) pathway, is required for signaling by nearly all RTKs (18–20).

We reconstitute a phosphotyrosine-mediated protein condensation phase transition of the ∼200 residue cytoplasmic tail of the epidermal growth factor receptor (EGFR) and the adaptor protein, Grb2, on a membrane surface.