Question

How is Focal Adhesion Kinase (FAK) connected to the MAPK pathway? I can never find answers for this. How EXACTLY does FAK lead to the activation of the MAPK pathway? Please no vague answers, I need to know what FAK binds, what it activates, where it goes, etc. in order to activate the MAPK pathway. I know that focal adhesion integrins bind to FAK....then what? Basically give me the steps between the activation of FAK and the activation of MAPKKK (also known as Raf: the first molecule in the MAPK pathway)

Answer 1

Focal Adhesion Kinase (FAK) is a protein kinase of 125 kDa act as a upstream regulator of the signaling cascades elicited by extracellular signals. It is activated by integrin-mediated adhesion between the integrin and the growth factor receptor signaling cascades. FAK plays a crucial role in integrin mediated cell spreading, differentiation, migration and migration. c-Src (Proto-oncogene tyrosine-protein kinase Src) is intimately involved in FAK-mediated signaling. C-src phosphorylate FAK at tyrosine (Tyr-925) phosphorylated in response to cell adhesion and there by binds to the Src homology 2 (SH2) of Grb2 (Growth factor receptor-bound protein 2, an adaptor protein involved in signal transduction) resulting in the activation of mitogen-activated protein kinase (MAPK). c-Src acts as a docking protein in FAK-mediated, integrin stimulation of MAPK.

C-src phosphorylate FAK at tyrosine (Tyr-925) phosphorylated in response to cell adhesion and there by binds to the Src homology 2 (SH2) of Grb2. Grb2 then binds to the guaninenucleotide exchange factor SOS and the activation of Ras. When the Grb2-SOS complex docks to phosphorylated FAK, SOS becomes activated. Activated SOS then promotes the removal of GDP from a member of the Ras subfamily and bind GTPand resulting in the activation of mitogen-activated protein kinase (MAPK).