1. Focal adhesion kinase promotes phospholipase C-γ1 activity
- Author
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Graham Carpenter, Steven K. Hanks, Qun-sheng Ji, Xiaoe Zhang, James D. Owen, Paul J. Ruest, and Ansuman Chattopadhyay
- Subjects
PTK2 ,Biology ,Transfection ,Proto-Oncogene Proteins c-myc ,Focal adhesion ,Mice ,chemistry.chemical_compound ,Cell Adhesion ,Animals ,Phosphorylation ,Glutathione Transferase ,Multidisciplinary ,PTK2B ,Phospholipase C gamma ,Autophosphorylation ,Tyrosine phosphorylation ,3T3 Cells ,Protein-Tyrosine Kinases ,Biological Sciences ,Embryo, Mammalian ,Peptide Fragments ,Recombinant Proteins ,Fibronectins ,Cell biology ,Enzyme Activation ,Isoenzymes ,chemistry ,Focal Adhesion Kinase 1 ,Focal Adhesion Protein-Tyrosine Kinases ,Type C Phospholipases ,COS Cells ,biological phenomena, cell phenomena, and immunity ,Cell Adhesion Molecules ,Tyrosine kinase ,Proto-oncogene tyrosine-protein kinase Src - Abstract
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.
- Published
- 1999