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

By David J. Sieg, C. Hauck, D. Ilić, C. Klingbeil, E. Schaefer, C. Damsky, D. Schlaepfer. Nature Cell Biology, 2000

1,321 citations recorded by the source corpus.

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 migration also requires FAK to be targeted, by its carboxy-terminal domain, to sites of integrin-receptor clustering. Although the kinase activity of FAK is not needed to promote PDGF- or EGF-stimulated cell motility, kinase-inactive FAK is transphosphorylated at the indispensable Src-kinase-binding site, FAK Y397, after EGF stimulation of cells. Our results establish that FAK is an important receptor-proximal link between growth-factor-receptor and integrin signalling pathways.

Subfields: Cell Biology, Hematology, Immunology and Allergy

View Paper: https://www.semanticscholar.org/paper/4f699fbae0a4e81cc3bfe20869b0ec1459bf0703

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In Cell Biology

1. J. Guan
2. Jihe Zhao
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4. A. Ullrich
5. J. Parsons

In Immunology and Allergy

1. J. Guan
2. Jihe Zhao
3. R. Juliano
4. J. Parsons

Citations in the corpus

• Focal Adhesion Kinase: a regulator of focal adhesion dynamics and cell movement (2000, background): “The Nterminal domain has recently been shown to direct the interaction of FAK with the activated forms of the Epidermal Growth Factor (EGF) receptor, although it is not clear whether such interactions are direct or via another protein(s) (Sieg et al., 2000).”
• Signaling pathways in cancer-associated fibroblasts and targeted therapy for cancer (2021, background): “In another study, it was shown that FUT8/CF in CAFs prompted the proliferation of cancer cells through EGFR signal cascade in non-small-cell lung cancer,251 suggesting that EGFR signaling in CAFs exerted a catalytic effect on CAF-mediated cancer progression and could be regulated by the CF modificat”
• Focal adhesion kinase: the first ten years (2003, background): “Most notably, FAK-deficient cells spread more slowly on extracellular matrix proteins, exhibit an increased number of prominent focal adhesions and migrate poorly in response to chemotactic and haptotactic signals (Ilic et al., 1995; Owen et al., 1999; Sieg et al., 2000; Sieg et al., 1999).”
• The epidermal growth factor receptor family as a central element for cellular signal transduction and diversification. (2001, background): “In a recent report, the focal adhesion kinase (FAK) has been demonstrated to link EGFR and integrin signalling pathways, thereby promoting EGF-induced cell migration independent of FAK’s intrinsic kinase activity (Sieg et al. 2000).”
• Signal transduction by cell adhesion receptors and the cytoskeleton: functions of integrins, cadherins, selectins, and immunoglobulin-superfamily members. (2002, background): “A very compelling recent report has proposed a coupling between integrins and RTKs via FAK (86).”