FAK integrates growth-factor and integrin signals to promote cell migration

@article{Sieg2000FAKIG,
  title={FAK integrates growth-factor and integrin signals to promote cell migration},
  author={David J. Sieg and Christof R. Hauck and Duško Ilić and Candice K. Klingbeil and Erik M. Schaefer and Caroline H. Damsky and David D. Schlaepfer},
  journal={Nature Cell Biology},
  year={2000},
  volume={2},
  pages={249-256}
}
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 re-expression of FAK rescues these defects. FAK associates with activated PDGF- and EGF-receptor (PDGFR and EGFR) signalling complexes, and expression of the band-4.1-like domain at the FAK amino terminus is sufficient to mediate an interaction with activated EGFR. However, efficient EGF-stimulated cell… 
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1,237 Citations
Highly Influential Citations
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1,237 Citations

Pyk2 and FAK regulate neurite outgrowth induced by growth factors and integrins
TLDR
It is shown that co-stimulation of growth-factor receptors and integrins activates the focal-adhesion kinase (FAK) family to promote outgrowth of neurites in PC12 and SH-SY5Y cells.
Focal Adhesion Kinase Facilitates Platelet-derived Growth Factor-BB-stimulated ERK2 Activation Required for Chemotaxis Migration of Vascular Smooth Muscle Cells*
TLDR
The results show that FAK inhibition by FRNK expression may provide a novel approach to regulate abnormal vascular SMC migration in vivo.
Matrix survival signaling: from fibronectin via focal adhesion kinase to c-Jun NH(2)-terminal kinase.
TLDR
It is reported that binding of the SH3 domain of p130Cas to proline-rich region 1 of FAK is required to support survival of fibroblasts on fibronectin when serum is withdrawn, and survival signals from extracellular matrix and serum are transduced by FAK via two distinct pathways.
Receptor Association to the Cytoskeleton and Integrins by Activating Src-Focal Adhesion Kinase and Induces Clustering of HER 2 β Transforming Growth Factor
TLDR
Data suggest that, by activating Src-FAK, TGF-B integrates ErbB receptor and integrin signaling to induce cell migration and survival during breast cancer progression.
MEK Kinase 1 Interacts with Focal Adhesion Kinase and Regulates Insulin Receptor Substrate-1 Expression*
TLDR
Findings indicate that MEKK1 interacts with FAK in focal adhesions and regulates IRS-1 expression, which appears to be physiologically relevant.
Control of motile and invasive cell phenotypes by focal adhesion kinase.
Direct Interaction of Focal Adhesion Kinase (FAK) with Met Is Required for FAK To Promote Hepatocyte Growth Factor-Induced Cell Invasion
TLDR
It is reported that FAK directly interacts with the hepatocyte growth factor receptor c-Met, providing evidence that constitutive Met-FAK interaction may be a critical determinant for tumor cells to acquire invasive potential.
Transforming growth factor beta induces clustering of HER2 and integrins by activating Src-focal adhesion kinase and receptor association to the cytoskeleton.
TLDR
Transforming growth factor beta induced focal adhesion kinase-dependent clustering of HER2 and integrins alpha(6), beta(1), and beta(4) in HER2-overexpressing mammary epithelial cells without altering the total and surface levels of Her2 receptors.
Focal adhesion kinase and its signaling pathways in cell migration and angiogenesis.
Matrix Survival Signaling
TLDR
It is reported that binding of the SH3 domain of p130Cas to proline-rich region 1 of FAK is required to support survival of fibroblasts on fibronectin when serum is withdrawn, and survival signals from extracellular matrix and serum are transduced by FAK via two distinct pathways.
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References

SHOWING 1-10 OF 50 REFERENCES
Required role of focal adhesion kinase (FAK) for integrin-stimulated cell migration.
TLDR
It is shown that stable re-expression of epitope-tagged FAK reversed the morphological defects of the FAK- cells through the dynamic regulation of actin structures and focal contact sites in fibronectin (FN) stimulated cells.
Signaling through focal adhesion kinase.
The association of focal adhesion kinase with a 200-kDa protein that is tyrosine phosphorylated in response to platelet-derived growth factor.
TLDR
The association of FAK with a 200-kDa protein (pp200) that is tyrosine phosphorylated in response to PDGF stimulation in NIH 3T3 cells is described, which may also be involved in growth-factor-induced cellular effects such as the modulation of cell adhesion or cell migration via cytoskeletal reorganization or disruption of focal adhesions.
Focal adhesion kinase promotes phospholipase C-γ1 activity
TLDR
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)-γ1 and that this is required for both adhesion-dependent association of the two molecules and increased inositol phosphate production in mouse embryo fibroblasts.
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
TLDR
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.
Identification of p130Cas as a Mediator of Focal Adhesion Kinase–promoted Cell Migration
TLDR
P130Cas, but not Grb2, is a mediator of FAK-promoted cell migration and it is suggested that FAK/ p130Cas complex targets downstream pathways other than Erks in mediatingFAK- Promoted Cell migration.
Association of Focal Adhesion Kinase with Grb7 and Its Role in Cell Migration*
TLDR
It is reported that the SH2 domain of Grb7 can directly interact with FAK through Tyr-397, a major autophosphorylation site in vitro and in vivo, suggesting that the FAK-Grb7 complex is involved in integrin signaling.
Integrins can collaborate with growth factors for phosphorylation of receptor tyrosine kinases and MAP kinase activation: roles of integrin aggregation and occupancy of receptors
TLDR
These studies identify mechanisms in the signal transduction response to integrins and growth factors that require various combinations of integrin aggregation and ligands for integrin or growth factor receptors, providing opportunities for collaboration between these major regulatory systems.
Multiple Grb2-Mediated Integrin-Stimulated Signaling Pathways to ERK2/Mitogen-Activated Protein Kinase: Summation of Both c-Src- and Focal Adhesion Kinase-Initiated Tyrosine Phosphorylation Events
TLDR
The studies show that FN receptor integrin signaling upstream of Ras and ERK2 does not follow a linear pathway but that, instead, multiple Grb2-mediated interactions with Shc, FAK, and perhaps other yet-to-be-determined phosphorylated targets represent parallel signaling pathways that cooperate to promote maximal ERK 2 activation.
Concerted Activity of Tyrosine Phosphatase SHP-2 and Focal Adhesion Kinase in Regulation of Cell Motility
TLDR
It is found that insulin-like growth factor I (IGF-I) induces the adhesion of MCF-7 to vitronectin and collagen in a dose- and time-dependent manner, suggesting that IGF-I triggers the activation of different integrins.
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