Abstract
BackgroundTks5/FISH is a scaffold protein comprising of five SH3 domains and one PX domain. Tks5 is a substrate of the tyrosine kinase Src and is required for the organization of podosomes/invadopodia implicated in invasion of tumor cells. Recent data have suggested that a close homologue of Tks5, Tks4, is implicated in the EGF signaling.ResultsHere, we report that Tks5 is a component of the EGF signaling pathway. In EGF-treated cells, Tks5 is tyrosine phosphorylated within minutes and the level of phosphorylation is sustained for at least 2 hours. Using specific kinase inhibitors, we demonstrate that tyrosine phosphorylation of Tks5 is catalyzed by Src tyrosine kinase. We show that treatment of cells with EGF results in plasma membrane translocation of Tks5. In addition, treatment of cells with LY294002, an inhibitor of PI 3-kinase, or mutation of the PX domain reduces tyrosine phosphorylation and membrane translocation of Tks5.ConclusionsOur results identify Tks5 as a novel component of the EGF signaling pathway.
Highlights
Tks5/FISH is a scaffold protein comprising of five SH3 domains and one Phox homology (PX) domain
We demonstrate that EGF-dependent tyrosine phosphorylation of Tks5 is catalyzed by Src tyrosine kinase
Tks5 is tyrosine phosphorylated in response to EGF Recently, we have shown that Tks4 is implicated in EGFdependent regulation of actin cytoskeleton [8,9], we have asked if Tks5, the homolog of Tks4, is involved directly in the EGF signaling pathway
Summary
Tks is a substrate of the tyrosine kinase Src and is required for the organization of podosomes/invadopodia implicated in invasion of tumor cells. The Frank-ter Haar syndrome protein Tks4/ HOFI/SH3PXD2B/fad (tyrosine kinase substrate with four SH3 domains / homolog of FISH / SH3 and PX domain-containing protein 2B / factor for adipocyte differentiation 49, hereafter termed Tks4) has emerged as a candidate scaffold molecule that has the capability to. Tks expression was required for protease-driven matrigel invasion in human cancer cells [17]. In this process Nck adaptor proteins, Nck and Nck, seem to link Tks to invadopodia actin regulation and extracellular matrix degradation [18]. Tks has been shown to be required for migration of neural crest cell during development of zebrafish embryos [19]
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