Inhibition of focal adhesion kinase (FAK) signaling in focal adhesions decreases cell motility and proliferation.

Gilmore, Andrew; Romer, Lewis H.

doi:10.1091/mbc.7.8.1209

Cited by 476 publications

(420 citation statements)

References 79 publications

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“…ECM: Extracellular matrix, RGD: Arg-Gly-Asp, JNK: Jun Kinase migrate less e ciently than control cells (Ilic et al, 1995). The observation that overexpression of FAK increases cell migration while a dominant negative form of the kinase inhibits it are also consistent with a role for this kinase in dynamic regulation of focal adhesions during cell migration (Cary et al, 1996;Gilmore and Romer, 1996).…”

Section: Focal Adhesion Kinasesupporting

confidence: 73%

Signaling by integrin receptors

Kumar¹

1998

Oncogene

253

181

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Adhesive interactions are critical for the proliferation, survival and function of all cells. Integrin receptors as the major family of adhesion receptors have been the focus of study for more than a decade. These studies have tremendously enhanced our understanding of the integrin-mediated adhesive interactions and have unraveled novel integrin functions in cell survival mechanisms and in the activation of divergent signaling pathways. The signals from integrin receptors are integrated from those originating from growth factor receptors in order to organize the cytoskeleton, stimulate cell proliferation and rescue cells from matrix detachment-induced programmed cell death. These functions are critical in the regulation of multiple processes such as tissue development, in¯ammation, angiogenesis, tumor cell growth and metastasis and programmed cell death.

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Section: Focal Adhesion Kinasesupporting

confidence: 73%

Signaling by integrin receptors

Kumar¹

1998

Oncogene

253

181

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“…In support of this hypothesis, treatment of fibroblasts with tyrosine kinase inhibitors blocks integrin-stimulated focal adhesion and stress fibre formation [15,22]. However, in contrast with this finding, it has been recently reported that FAK activity might play a more important role in cell migration than in focal adhesion assembly [23].…”

Section: Introductionmentioning

confidence: 92%

Adhesion of fibroblasts to fibronectin stimulates both serine and tyrosine phosphorylation of paxillin

Bellis

Perrotta

Curtis

et al. 1997

Biochemical Journal

110

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Tyrosine phosphorylation of paxillin by the focal adhesion kinase (FAK) has been implicated as a signal transduction mechanism associated with cell adhesion and cytoskeletal reorganization. The potential role of serine phosphorylation of paxillin in these events has not been well characterized. In this study we have examined the phosphorylation profile of paxillin both invitro and invivo. By using glutathione S-transferase–paxillin fusion proteins in precipitation-kinase assays invitro we observed that a fusion protein spanning amino acid residues 54–313 of paxillin, and containing a FAK-binding site, precipitated substantial serine kinase activity as well as FAK activity from a smooth-muscle lysate. Together these kinases phosphorylated paxillin on tyrosine residue 118, a site that has been identified previously as a target for FAK phosphorylation, and on serine residues 188 and/or 190. The binding site for the serine kinase, the identity of which is currently unknown, was further mapped to residues 168–191 of paxillin. To assess the physiological relevance of these sites phosphorylated invitro, the profile of paxillin phosphorylation invivo stimulated by seeding fibroblasts on fibronectin was characterized. As expected, plating cells on fibronectin enhanced the tyrosine phosphorylation of paxillin. However, 96% of the phosphorylation of paxillin occurred on serine residues. Comparison by two-dimensional phosphopeptide analyses indicated that the major sites of tyrosine and serine phosphorylation detected in the assays invitro co-migrate with phosphopeptides derived from paxillin phosphorylated invivo in response to plating cells on fibronectin. These findings support a role for both tyrosine and serine kinases in the signal transduction pathway linking integrin activation to paxillin phosphorylation.

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“…GST-fusion proteins were expressed and purified from Escherichia coli onto glutathione agarose as previously described (Gilmore and Romer, 1996). Transiently transfected cells were lysed in NET buffer and incubated with 40 μl (50 % slurry) of the purified GST-fusion protein-coated glutathione-agarose (4°C/2 hours).…”

Section: Gst Fusion Proteins Pull Down Assaysmentioning

confidence: 99%

FAK engages multiple pathways to maintain survival of fibroblasts and epithelia – differential roles for paxillin and p130Cas

Zouq

Keeble

Lindsay

et al. 2009

Journal of Cell Science

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survival signalling in cell types from distinct embryonic lineages that show differing sensitivities to anoikis. We demonstrate that both fibroblasts and epithelial cells prevent anoikis through FAK activation. We show that FAK activates multiple downstream pathways in order to suppress anoikis. However FAK regulates survival through a more restricted set of pathways in the more anoikis-sensitive epithelial cells. Furthermore, we identify a novel role for paxillin in apoptosis suppression.

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Inhibition of focal adhesion kinase (FAK) signaling in focal adhesions decreases cell motility and proliferation.

Cited by 476 publications

References 79 publications

Signaling by integrin receptors

Signaling by integrin receptors

Adhesion of fibroblasts to fibronectin stimulates both serine and tyrosine phosphorylation of paxillin

FAK engages multiple pathways to maintain survival of fibroblasts and epithelia – differential roles for paxillin and p130Cas

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