Preparing your results

Our searching services are busy right now. Your search will reload in five seconds.

X
Forgot Password

If you have forgotten your password you can enter your email here and get a temporary password sent to your email.

Focal adhesion kinase promotes phospholipase C-gamma1 activity.

http://www.ncbi.nlm.nih.gov/pubmed/10430888

The nonreceptor tyrosine kinase FAK ("focal adhesion kinase") is a key mediator of integrin signaling events controlling cellular responses to the extracellular matrix, including spreading, migration, proliferation, and survival. Integrin-ligand interactions stimulate FAK tyrosine phosphorylation and activation of FAK signaling functions. Here evidence is presented that the FAK autophosphorylation site Tyr-397 mediates a direct interaction with the C-terminal Src homology 2 domain of phospholipase C (PLC)-gamma1 and that this is required for both adhesion-dependent association of the two molecules and increased inositol phosphate production in mouse embryo fibroblasts. Overexpression of FAK and PLC-gamma1 in COS-7 cells increases PLC-gamma1 enzymatic activity and tyrosine phosphorylation, also dependent on FAK Tyr-397. However, FAK appears incapable of directly phosphorylating PLC-gamma1. These observations suggest a role for FAK in recruiting PLC-gamma1 to the plasma membrane at sites of cell-matrix adhesion and there promoting its enzymatic activity, possibly by releasing the repression caused by intramolecular interactions of the PLC-gamma1 Src homology domains and/or by positioning it for phosphorylation by associated Src-family kinases. These findings expand the known signaling functions of FAK and provide mechanistic insight into integrin-stimulation of PLC-gamma1.

Pubmed ID: 10430888 RIS Download

Mesh terms: 3T3 Cells | Animals | COS Cells | Cell Adhesion | Cell Adhesion Molecules | Embryo, Mammalian | Enzyme Activation | Fibronectins | Focal Adhesion Kinase 1 | Focal Adhesion Protein-Tyrosine Kinases | Glutathione Transferase | Isoenzymes | Mice | Peptide Fragments | Phospholipase C gamma | Phosphorylation | Protein-Tyrosine Kinases | Proto-Oncogene Proteins c-myc | Recombinant Proteins | Transfection | Type C Phospholipases