Focal adhesion kinase promotes phospholipase C-γ1 activity

  title={Focal adhesion kinase promotes phospholipase C-$\gamma$1 activity},
  author={Xiaoe Zhang and Ansuman Chattopadhyay and Qun-sheng Ji and James D. Owen and Paul J. Ruest and Graham F. Carpenter and Steven K. Hanks},
  journal={Proceedings of the National Academy of Sciences of the United States of America},
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… 
Integrin-dependent PLC-γ1 phosphorylation mediates fibronectin-dependent adhesion
The data demonstrated that PLC-γ1 co-immunoprecipitated with Src following fibronectin-induced integrin activation, and this association did not depend on FAK expression.
[Focal adhesion kinase (FAK), a multifunctional protein].
The mechanisms by which FAK transmits biochemical signals and elicits biological effects, including motility, survival and proliferation, are focused upon.
Regulation of focal adhesion kinase by a novel protein inhibitor FIP200.
Results identify FIP200 as a novel protein inhibitor for FAK, which is decreased upon integrin-mediated cell adhesion concomitant with FAK activation and leads to increased FAK phosphorylation and partial restoration of cell cycle progression in cells plated on poly-L-lysine, providing further support for FIP 200 as a negative regulator of FAK.
Phosphospecific antibodies reveal focal adhesion kinase activation loop phosphorylation in nascent and mature focal adhesions and requirement for the autophosphorylation site.
These findings support a model for reciprocal activation of FAK and Src-family kinases and suggest that FAK/Src signaling may occur during both focal adhesion assembly and turnover.
FAK integrates growth-factor and integrin signals to promote cell migration
Here we show that cells lacking focal adhesion kinase (FAK) are refractory to motility signals from platelet-derived and epidermal growth factors (PDGF and EGF respectively), and that stable
Regulation of focal adhesion dynamics and disassembly by phosphorylation of FAK at tyrosine 397
The data show that phosphorylation of FAK at Tyr-397 is a key determinant of how FAK controls focal adhesion turnover and induces disassembly of focal adhesions at the cell tail and promotes cell motility as shown by the decrease in microtubule-mediated turnover of Y397F-FAK/YCam-containing focalAdhesions.
Src Catalytic but Not Scaffolding Function Is Needed for Integrin-Regulated Tyrosine Phosphorylation, Cell Migration, and Cell Spreading
ABSTRACT Src family kinases (SFKs) are crucial for signaling through a variety of cell surface receptors, including integrins. There is evidence that integrin activation induces focal adhesion kinase
Src Family Kinases Are Required for Integrin-mediated but Not for G Protein-coupled Receptor Stimulation of Focal Adhesion Kinase Autophosphorylation at Tyr-397*
The results identify, for first time, the existence of Src-dependent and SRC-independent pathways leading to FAK autophosphorylation at Tyr-397 stimulated by adhesion-dependent signals and G protein-coupled receptor agonists in the same cell.
The mechanism involved in the regulation of phospholipase Cγ1 activity in cell migration
It is found that EGF induces a PI 3-K-dependent translocation of PLCγ1 at the leading edge of migrating cells in a wound healing assay and stable PH P LCγ1 expression blocks epidermal growth factor- and serum-induced cell motility and increases cell adhesion in MDA-MB-231 cells.


Signaling through focal adhesion kinase
  • S. Hanks, T. Polte
  • Biology
    BioEssays : news and reviews in molecular, cellular and developmental biology
  • 1997
This work has shown that recruitment of proteins containing Src homology 2 domains, including Grb2 and c‐Crk, to the complex is likely to trigger adhesion‐induced cellular responses, including changes to the actin cytoskeleton and activation of the Ras‐MAP kinase pathway.
Phosphorylation of Tyrosine 397 in Focal Adhesion Kinase Is Required for Binding Phosphatidylinositol 3-Kinase*
It is suggested that FAK activation and autophosphorylation at Tyr-397 may lead to its association with PI 3-kinase through the SH2 domains of p85, which can subsequently activate PI 3 -kinase during cell adhesion.
Induced Focal Adhesion Kinase (FAK) Expression in FAK-Null Cells Enhances Cell Spreading and Migration Requiring Both Auto- and Activation Loop Phosphorylation Sites and Inhibits Adhesion-Dependent Tyrosine Phosphorylation of Pyk2
It is demonstrated that both the FAK autophosphorylation and activation loop sites are critical for maximum adhesion-induced FAK activation and FAK-enhanced cell spreading and migration responses.
Stimulation of cell migration by overexpression of focal adhesion kinase and its association with Src and Fyn.
It is reported here that overexpression of FAK in CHO cells increased their migration on fibronectin, and a mutation of the major autophosphorylation site Y397 in FAK abolished its ability to stimulate cell migration, while phosphorylation in a kinase-defective FAK by endogenous FAK led to increased migration.
Integrin-mediated signal transduction linked to Ras pathway by GRB2 binding to focal adhesion kinase
It is shown that adhesion of murine NIH3T3 fibroblasts to fibronectin promotes SH2-domain-mediated association of the GRB2 adaptor protein and the c-Src protein-tyrosine kinase (PTK) with FAK in vivo, and also results in activation of mitogen-activated protein Kinase (MAPK).
Focal adhesion kinase and phospholipase C gamma involvement in adhesion and migration of human hepatic stellate cells.
Findings provide the first evidence that PLC gamma recruitment by FAK during HSCAdhesion is an important process implicating a link between integrin and PDGF-mediated signaling pathways to regulate HSC adhesion and motility.
Fibronectin-stimulated signaling from a focal adhesion kinase-c-Src complex: involvement of the Grb2, p130cas, and Nck adaptor proteins
Results show that there are additional FN-stimulated pathways to ERK2 that do not involve Grb2 binding to FAK, and FAK-induced phosphorylation of p130cas in the Src 1-298 cells promoted the SH2 domain-dependent binding of the Nck adaptor protein to p 130cas, which may facilitate signaling to ERk2.
Complexes of Focal Adhesion Kinase (FAK) and Crk-associated Substrate (p130Cas) Are Elevated in Cytoskeleton-associated Fractions following Adhesion and Src Transformation
These findings firmly establish a direct interaction between FAK and Cas and demonstrate that Src can influence the subcellular localization of the complex by a tyrosine phosphorylation-dependent mechanism.
Integrin-Induced Protein Kinase Cα and Cε Translocation to Focal Adhesions Mediates Vascular Smooth Muscle Cell Spreading
The results show that integrins induce intracellular signaling in VSMCs via DAG and PKC, and both isoforms seem to play a role in inside-out integrin signaling and cell spreading.
Tyrosine phosphorylation of focal adhesion kinase at sites in the catalytic domain regulates kinase activity: a role for Src family kinases
It is found that maximal kinase activity of FAK immune complexes requires phosphorylation of both tyrosines 576 and 577, which indicates that phosphorylated by Src (or other Src family kinases) is an important step in the formation of an active signaling complex.