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Fig. 11 | Cell Communication and Signaling

Fig. 11

From: The multi-site docking protein Grb2-associated binder 1 (Gab1) enhances interleukin-6-induced MAPK-pathway activation in an SHP2-, Grb2-, and time-dependent manner

Fig. 11

Initiation- and amplification-phase model of IL-6-induced Erk1/2 pathway activation. Initial ligand-induced activation of gp130 leads to phosphorylation of tyrosine residues in gp130, enabling recruitment of SHP2 to phosphorylated tyrosine 759 to activate the Erk1/2 pathway in the initiation phase. Activated Erk phosphorylates serine 552 within Gab1. This phosphorylation releases the intramolecular block of the PH domain and enables recruitment of Gab1 to PIP3 at the plasma membrane. Gab1 recruited at the plasma membrane becomes tyrosine phosphorylated. Phosphorylated tyrosine 627 and 659 within Gab1 serve as binding sites for SHP2. Activation of Erk1/2 in the Gab1-dependent amplification phase requires binding of SHP2 and Grb2 to Gab1. Furthermore, binding of SHP2 to Gab1 depends on binding of Grb2 to Gab1

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