PKC-Dependent Activation of FAK and Src Induces Tyrosine Phosphorylation of Cas and Formation of Cas–Crk Complexes

Bruce-Staskal, Pamela J.; Bouton, Amy H.

doi:10.1006/excr.2000.5137

Cited by 40 publications

(35 citation statements)

References 77 publications

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“…Involvement of a tyrosine kinase upstream of IKK activation has also been reported in CD23 signaling in U937 cells (32) and in Ag receptor stimulation in B cell (33). A similar PKC-dependent c-Src activation pathway has been found in human osteoblasts (36), in which fibroblast growth factor-2 increases N-cadherin expression; in A7r5 vascular smooth muscle cells (37), in which TPA induces Rho-dependent actin reorganization; and in SH-SY5Y neuroblastoma cells (38), in which TPA induces CasCrk complex formation. Furthermore, the PKC/c-Src/IKK pathway, in this study shown to be involved in induction of COX-2 expression, might be a common signaling pathway for inducible gene expression, as TNF-␣-, IL-1␤-, or IFN-␥-induced ICAM-1 expression in human alveolar epithelial cells also involves PKCdependent activation of c-Src or Lyn (26, 39 -41).…”

Section: Discussionmentioning

confidence: 52%

Tyrosine Phosphorylation of I-κB Kinase α/β by Protein Kinase C-Dependent c-Src Activation Is Involved in TNF-α-Induced Cyclooxygenase-2 Expression

Huang

Chen

Inoue

et al. 2003

The Journal of Immunology

117

106

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The signaling pathway involved in TNF-α-induced cyclooxygenase-2 (COX-2) expression was further studied in human NCI-H292 epithelial cells. A protein kinase C (PKC) inhibitor (staurosporine), tyrosine kinase inhibitors (genistein and herbimycin A), or a Src kinase inhibitor (PP2) attenuated TNF-α- or 12-O-tetradecanoylphorbol-13-acetate (TPA)-induced COX-2 promoter activity. TNF-α- or TPA-induced I-κB kinase (IKK) activation was also blocked by these inhibitors, which reversed I-κBα degradation. Activation of c-Src and Lyn kinases, two Src family members, was inhibited by the PKC, tyrosine kinase, or Src kinase inhibitors. The dominant-negative c-Src (KM) mutant inhibited induction of COX-2 promoter activity by TNF-α or TPA. Overexpression of the constitutively active PKCα (PKCα A/E) or wild-type c-Src plasmids induced COX-2 promoter activity, and these effects were inhibited by the dominant-negative c-Src (KM), NF-κB-inducing kinase (NIK) (KA), or IKKβ (KM) mutant. The dominant-negative PKCα (K/R) or c-Src (KM) mutant failed to block induction of COX-2 promoter activity caused by wild-type NIK overexpression. In coimmunoprecipitation experiments, IKKα/β was found to be associated with c-Src and to be phosphorylated on its tyrosine residues after TNF-α or TPA treatment. Two tyrosine residues, Tyr188 and Tyr199, near the activation loop of IKKβ, were identified to be crucial for NF-κB activation. Substitution of these residues with phenylalanines attenuated COX-2 promoter activity and c-Src-dependent phosphorylation of IKKβ induced by TNF-α or TPA. These data suggest that, in addition to activating NIK, TNF-α also activates PKC-dependent c-Src. These two pathways cross-link between c-Src and NIK and converge at IKKα/β, and go on to activate NF-κB, via serine phosphorylation and degradation of IκB-α, and, finally, to initiate COX-2 expression.

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Section: Discussionmentioning

confidence: 52%

Tyrosine Phosphorylation of I-κB Kinase α/β by Protein Kinase C-Dependent c-Src Activation Is Involved in TNF-α-Induced Cyclooxygenase-2 Expression

Huang

Chen

Inoue

et al. 2003

The Journal of Immunology

117

106

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“…In the present paper, we have demonstrated that Wnt-5a is involved in the activation of FAK, the turnover of paxillin and membrane ruffling. It has also been shown that Wnt-5a activates PKC [7] and that JNK-dependent phosphorylation of paxillin and PKC-dependent activation of FAK are important for cell migration [37,38]. These findings suggest that Wnt-5a activates PKC and JNK, thereby leading to the activation of FAK.…”

Section: Activities Of Wnt-5amentioning

confidence: 88%

Post-translational palmitoylation and glycosylation of Wnt-5a are necessary for its signalling

Kurayoshi

Yamamoto

Izumi

et al. 2007

Biochemical Journal

208

215

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Wnt-5a is a representative ligand that activates a β-catenin-independent pathway in Wnt signalling. In the present paper, the roles of the post-translational modifications in the actions of Wnt-5a were investigated. We found that Wnt-5a is modified with palmitate at Cys 104 and glycans at Asn 114 , Asn 120 , Asn 311 and Asn 325 . The palmitoylation was not essential for the secretion of Wnt-5a, but was necessary for its ability to suppress Wnt-3a-dependent Tcell factor transcriptional activity and to stimulate cell migration. Wnt-5a activated focal adhesion kinase and this activation also required palmitoylation. Wild-type Wnt-5a induced the internalization of Fz (Frizzled) 5, but a Wnt-5a mutant that lacks the palmitoylation site did not. Furthermore, the binding of Wnt5a to the extracellular domain of Fz5 required palmitoylation of Wnt-5a. These results indicate that palmitoylation of Wnt-5a is important for the triggering of signalling at the cell surface level and, therefore, that the lipid-unmodified form of Wnt-5a cannot activate intracellular signal cascades. In contrast, glycosylation was necessary for the secretion of Wnt-5a, but not essential for the actions of Wnt-5a. Thus the post-translational palmitoylation and glycosylation of Wnt-5a are important for the actions and secretion of Wnt-5a.

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“…Protein Kinase C Activity Is Not Involved in Regulating Phosphorylation of FAK Tyr 397 -Protein kinase C activation precedes cell spreading on FN and its stimulation has been shown to increase FN-mediated cell adhesion (66,67). Direct activation of PKC by the phorbol ester PMA has been shown to stimulate focal adhesion formation (68) and FAK tyrosine phosphorylation (69). Recruitment of syndecan-4 to focal adhesions is dependent on PKC (18), and syndecan-4, in turn, modulates PKC localization and activity through the binding intermediary phosphatidylinositol bisphosphate (11,12).…”

mentioning

confidence: 99%

Syndecan-4 Modulates Focal Adhesion Kinase Phosphorylation

Wilcox-Adelman¹,

Denhez

Goetinck

2002

Journal of Biological Chemistry

123

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PKC-Dependent Activation of FAK and Src Induces Tyrosine Phosphorylation of Cas and Formation of Cas–Crk Complexes

Cited by 40 publications

References 77 publications

Tyrosine Phosphorylation of I-κB Kinase α/β by Protein Kinase C-Dependent c-Src Activation Is Involved in TNF-α-Induced Cyclooxygenase-2 Expression

Tyrosine Phosphorylation of I-κB Kinase α/β by Protein Kinase C-Dependent c-Src Activation Is Involved in TNF-α-Induced Cyclooxygenase-2 Expression

Post-translational palmitoylation and glycosylation of Wnt-5a are necessary for its signalling

Syndecan-4 Modulates Focal Adhesion Kinase Phosphorylation

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