Regulation of focal adhesion-associated protein tyrosine kinase by both cellular adhesion and oncogenic transformation

Guan, Jun‐Lin; Shalloway, David

doi:10.1038/358690a0

Cited by 781 publications

(504 citation statements)

References 14 publications

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“…Phosphorylation of tyrosine residues of FAK is stimulated in the cells transformed by pp60 ..... , or by attachment of cells to fibronectin or other celladhesive proteins [1][2][3][4][5][6]. Tyrosine kinase activity of FAK is regulated, at least in part, by the phosphorylation of tyrosine residues of FAK [7].…”

Section: Introduction 2 Materials and Methodsmentioning

confidence: 99%

Possible role of protein kinase C in the regulation of intracellular stability of focal adhesion kinase in mouse 3T3 cells

Mogi

Hatai²,

Soga³

et al. 1995

FEBS Letters

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Key words: Calphostin C; Focal adhesion kinase; FAK; Protein kinase C; Fibronectin; Phosphorylation protein, and that the phosphorylation of FAK at Tyr-925 was involved in the activation of Ras/MAP kinase signal transduction pathway [10,11]. Thus, tyrosine-phosphorylation of FAK seems to regulate its interaction with other proteins in the signal transduction pathways, as well as its protein kinase activity.On the other hand, it has been established that serine, not only tyrosine, residues in FAK are phosphorylated by the attachment of cells to fibronectin [9,12]. Activation of protein kinase C causes the stimulation of cell attachment, spreading, and tyrosine-phosphorylation of FAK [13,14]. Attachment of cells to fibronectin causes rapid and transient activation of protein kinase C, so serine-phosphorylation might be a prerequisite for tyrosine-phosphorylation of FAK [14]. These findings suggest that phosphorylation of serine residues in FAK may regulate the biological activities of FAK, but the mechanism and physiological roles of serine-phosphorylation of FAK are not fully understood.In the present study, we have examined the effects of various types of protein kinase inhibitor on the adhesion and spreading of BALB/c mouse 3T3 cells, and on the phosphorylation and stability of FAK in the cells. Here, we reported that the serinephosphorylation of FAK induced by protein kinase C might be important in the regulation of intracellular stability of FAK.

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Section: Introduction 2 Materials and Methodsmentioning

confidence: 99%

Possible role of protein kinase C in the regulation of intracellular stability of focal adhesion kinase in mouse 3T3 cells

Mogi

Hatai²,

Soga³

et al. 1995

FEBS Letters

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“…Activation of src or Met promotes invasiveness through the destabilization of intercellular junctions, e.g. integrins-FAK and cadherins-catenin adhesion complexes (Guan and Shalloway, 1992).…”

Section: Expression Of Apc E-cadherin and Associated Proteinsmentioning

confidence: 99%

“…We therefore characterized the tumorigenic potential and the pattern of differentiation and proliferation of these transfected PC AA/C I cell derivatives. Since both APC and pp6Osr have been shown to be localized or associated with cell-cell adhesion effectors or cytoskeletal components, we investigated the invasive phenotype of the parental and transfected PC cell lines in relation to the expression of the receptor, tyrosine kinase Met, and its ligand hepatocyte growth factor / scatter factor (HGF/SF) as known effectors of invasion (Guan and Shalloway, 1992;Rubinfield et al, 1993;Rosen et al, 1994;Smith et al, 1994). We also analysed the expression and phosphorylation status of the E-cadherin-catenin cell adhesion complex binding the tyrosine kinase substrate pl20" (Daniel and Reynolds, 1995).…”

mentioning

confidence: 99%

Progression of familial adenomatous polyposis (FAP) colonic cells after transfer of the src or polyoma middle T oncogenes: cooperation between src and HGF/Met in invasion

et al. 1997

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Summary Little is known about the the signalling pathways driving the adenoma-to-carcinoma sequence in human colonic epithelial cells. Accumulation and activation of the src tyrosine kinase in colon cancer suggest a potential role of this oncogene in this early progression. Therefore, we introduced either activated src (m-src), polyoma-MT alone or combined with normal c-src in the adenoma PC/AA/C1 cell line (PC) to define the function and phenotypic transformations induced by these oncogenes in familial adenomatous polyposis (FAP) colonic epithelial cells. Functional expression of these oncoproteins induced the adenoma-to-carcinoma conversion, overexpression of the hepatocyte growth factor (HGF) receptor Met, but failed to confer invasiveness in vivo and in vitro, or to produce alterations in cell proliferation and differentiation. In contrast, PC-msrc cells became susceptible to the HGF-induced invasion of collagen gels and exhibited sustained activation of the pp6osrctyrosine kinase and Tyr phosphorylation of the 120-kDa E-cadherin, which was further increased by HGF Transcripts of HGF were clearly identified by reverse transcription -polymerase chain reaction (RT-PCR) and Southern blot in the parental and transformed PC cells, suggesting an autocrine mechanism. Taken together, the data indicate that: (1) experimental activation of src and PyMT pathways directly induces tumorigenicity and Met upregulation in a colon adenoma cell line; (2) HGF-activated Met and src cooperate in inducing invasion; (3) in view of the molecular associations between catenins and cadherin or the tumour-suppressor gene product APC, the cell adhesion molecule E-cadherin may constitute a downstream effector of src and Met.

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“…FAK was originally identified as a substrate of Src and subsequently found to be activated upon cell adhesion to extracellular matrix proteins (Guan and Shalloway, 1992;Hanks et al, 1992;Schaller et al, 1992). Later, it was also found to be activated by a number of growth factors (Matsumoto et al, 1994;Rankin and Rozengurt, 1994;Chen et al, 1998;Sieg et al, 2000).…”

Section: Introductionmentioning

confidence: 99%

Phosphorylation of focal adhesion kinase on tyrosine 194 by Met leads to its activation through relief of autoinhibition

et al. 2010

Oncogene

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Focal adhesion kinase (FAK) has a crucial role in integration of signals from integrins and growth factor receptors. In this study, we demonstrate that growth factor receptors including hepatocyte growth factor receptor Met, epidermal growth factor receptor, and platelet-derived growth factor receptor directly phosphorylate FAK on Tyr194 in the FERM domain (band 4.1 and ezrin/radixin/moesin homology domain). Upon binding to Met or phosphoinositides, FAK may undergo conformational changes, which renders Tyr194 accessible for phosphorylation. Substitution of Tyr194 with Phe significantly suppresses the activation of FAK by Met. In contrast, substitution of Tyr194 with Glu (Y194E substitution) leads to constitutive activation of FAK. The phosphorylation of FAK on Tyr194 may cause conformational changes in the FERM domain, which disrupts the intramolecular inhibitory interaction between the FERM and kinase domains of FAK. Moreover, substitution of the basic residues in the 216 KAKTLRK 222 patch in the FERM domain with Ala antagonizes the effect of the Y194E substitution on FAK activation, thus suggesting that the interactions between the phosphorylated Tyr194 and the basic resides in the 216 KAKTLRK 222 patch may allow FAK to be activated through relief of its autoinhibition. Collectively, this study provides the first example to explain how FAK is activated by receptor tyrosine kinases.

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Regulation of focal adhesion-associated protein tyrosine kinase by both cellular adhesion and oncogenic transformation

Cited by 781 publications

References 14 publications

Possible role of protein kinase C in the regulation of intracellular stability of focal adhesion kinase in mouse 3T3 cells

Possible role of protein kinase C in the regulation of intracellular stability of focal adhesion kinase in mouse 3T3 cells

Progression of familial adenomatous polyposis (FAP) colonic cells after transfer of the src or polyoma middle T oncogenes: cooperation between src and HGF/Met in invasion

Phosphorylation of focal adhesion kinase on tyrosine 194 by Met leads to its activation through relief of autoinhibition

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