Phosphoinositide 3-Kinase-mediated Activation of Cofilin Phosphatase Slingshot and Its Role for Insulin-induced Membrane Protrusion

Michiru Nishita, Yan Wang, Chinatsu Tomizawa, Akira Suzuki, Ryusuke Niwa, Tadashi Uemura, Kensaku Mizuno

Research output: Contribution to journalArticlepeer-review

95 Citations (Scopus)


Cofilin plays an essential role in actin filament dynamics and membrane protrusion in motile cells. Cofilin is inactivated by phosphorylation at Ser-3 by LIM kinase and reactivated by dephosphorylation by cofilin-phosphatase Slingshot (SSH). Although cofilin is dephosphorylated in response to various extracellular stimuli, signaling pathways regulating SSH activation and cofilin dephosphorylation have remained to be elucidated. Here we show that insulin stimulates the phosphatase activity of Slingshot-1L (SSH1L) and cofilin dephosphorylation in cultured cells, in a manner dependent on phosphoinositide 3-kinase (PI3K) activity. Consistent with this, the level of Ser-3-phosphorylated cofilin is increased in PTEN (phosphatase and tensin homolog deleted in chromosome 10)-overexpressing cells and decreased in PTEN-deficient cells. Insulin induced the accumulation of SSH1L and active Akt (a downstream effector of PI3K), together with a PI3K product phosphatidylinositol 3,4,5-trisphosphate, onto membrane protrusions. Cofilin, but not Ser-3-phosphorylated cofilin, accumulated in membrane protrusions in insulin-stimulated cells, indicating that cofilin is dephosphorylated in these areas. Finally, suppression of SSH1L expression by RNA interference abolished insulin-induced cofilin dephosphorylation and the membrane protrusion. These findings suggest that SSH1L is activated downstream of PI3K and plays a critical role in insulin-induced membrane, protrusion by dephosphorylating and activating cofilin.

Original languageEnglish
Pages (from-to)7193-7198
Number of pages6
JournalJournal of Biological Chemistry
Issue number8
Publication statusPublished - 2004 Feb 20

ASJC Scopus subject areas

  • Biochemistry
  • Molecular Biology
  • Cell Biology


Dive into the research topics of 'Phosphoinositide 3-Kinase-mediated Activation of Cofilin Phosphatase Slingshot and Its Role for Insulin-induced Membrane Protrusion'. Together they form a unique fingerprint.

Cite this