Frank-ter Haar syndrome protein Tks4 regulates epidermal growth factor-dependent cell migration

Gábor Bögel, Annamária Gujdár, Miklós Geiszt, Árpád Lányi, Anna Fekete, Szabolcs Sipeki, Julian Downward, László Buday

Research output: Contribution to journalArticle

17 Citations (Scopus)

Abstract

Mutations in the SH3PXD2B gene coding for the Tks4 protein are responsible for the autosomal recessive Frank-ter Haar syndrome. Tks4, a substrate of Src tyrosine kinase, is implicated in the regulation of podosome formation. Here, we report a novel role for Tks4 in the EGF signaling pathway. In EGF-treated cells, Tks4 is tyrosine-phosphorylated and associated with the activated EGF receptor. This association is not direct but requires the presence of Src tyrosine kinase. In addition, treatment of cells with LY294002, an inhibitor of PI 3-kinase, or mutations of the PX domain reduces tyrosine phosphorylation and membrane translocation of Tks4. Furthermore, a PX domain mutant (R43W) Tks4 carrying a reported point mutation in a Frank-ter Haar syndrome patient showed aberrant intracellular expression and reduced phosphoinositide binding. Finally, silencing of Tks4 was shown to markedly inhibit HeLa cell migration in a Boyden chamber assay in response to EGF or serum. Our results therefore reveal a new function for Tks4 in the regulation of growth factor-dependent cell migration.

Original languageEnglish
Pages (from-to)31321-31329
Number of pages9
JournalJournal of Biological Chemistry
Volume287
Issue number37
DOIs
Publication statusPublished - Sep 7 2012

ASJC Scopus subject areas

  • Biochemistry
  • Molecular Biology
  • Cell Biology

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