Sprouty-4 negatively regulates cell spreading by inhibiting the kinase activity of testicular protein kinase

Yoshikazu Tsumura, Jiro Toshima, Onno C. Leeksma, Kazumasa Ohashi, Kensaku Mizuno

Research output: Contribution to journalArticlepeer-review

31 Citations (Scopus)

Abstract

TESK1 (testicular protein kinase 1) is a serine/threonine kinase that phosphorylates cofilin and plays a critical role in integrin-mediated actin cytoskeletal reorganization and cell spreading. We previously showed that TESK1 interacts with Sprouty-4 (referred to as Spry4), an inhibitor of growth factor-induced Ras/MAP (mitogen-activated protein) kinase signalling, but the functional role of this interaction has remained unknown. In the present study, we show that Spry4 inhibits the kinase activity of TESK1 by binding to it through the C-terminal cysteine-rich region. Expression of Spry4 in cultured cells suppressed integrin-mediated cell spreading, and TESK1 reversed the inhibitory effect of Spry4 on cell spreading. Furthermore, Spry4 suppressed integrin- and TESK1-mediated cofilin phosphorylation during the spreading of cells on laminin. These findings suggest that Spry4 suppresses cell spreading by inhibiting the kinase activity of TESK1. Although tyrosine phosphorylation is required for the inhibitory activity of Spry4 on a Ras/MAP kinase pathway, mutation of the corresponding tyrosine residue (Tyr-75 in human Spry4) to an alanine had no apparent effect on its inhibitory actions on TESK1 activity and cell spreading, which suggests a novel cellular function of Spry to regulate the actin cytoskeleton, independent of its inhibitory activity on the Ras/MAP kinase signalling.

Original languageEnglish
Pages (from-to)627-637
Number of pages11
JournalBiochemical Journal
Volume387
Issue number3
DOIs
Publication statusPublished - 2005 May 1

Keywords

  • Cell spreading
  • Cofilin
  • Laminin
  • Mitogen-activated protein kinase (MAP kinase)
  • Sprouty
  • Testicular protein kinase (TESK)

ASJC Scopus subject areas

  • Biochemistry
  • Molecular Biology
  • Cell Biology

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