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Focal adhesion kinase promotes phospholipase C-gamma1 activity.

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


  • Zhang X
  • Chattopadhyay A
  • Ji QS
  • Owen JD
  • Ruest PJ
  • Carpenter G
  • Hanks SK


Proceedings of the National Academy of Sciences of the United States of America

Publication Data

August 3, 1999

Associated Grants

  • Agency: NCI NIH HHS, Id: CA75195
  • Agency: NIGMS NIH HHS, Id: GM49882

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