14-3-3 regulates actin dynamics by stabilizing phosphorylated cofilin

Curr Biol. 2002 Oct 1;12(19):1704-10. doi: 10.1016/s0960-9822(02)01184-3.


The functionality of the actin cytoskeleton depends on a dynamic equilibrium between filamentous and monomeric actin. Proteins of the ADF/cofilin family are essential for the high rates of actin filament turnover observed in motile cells through regulation of actin polymerization/depolymerization cycles. Rho GTPases act through p21-activated kinase-1 (Pak-1) and Rho kinase to inhibit cofilin activity via the LIM kinase (LIMK)-mediated phosphorylation of cofilin on Ser3. We report the identification of 14-3-3zeta as a novel phosphocofilin binding protein involved in the maintenance of the cellular phosphocofilin pool. A Ser3 phosphocofilin binding protein was purified from bovine brain and was identified as 14-3-3zeta by mass spectrometry. The phosphorylation-dependent interaction between cofilin and 14-3-3zeta was confirmed in pulldown and coimmunoprecipitation experiments. Both Ser3 phosphorylation and a 14-3-3 recognition motif in cofilin are necessary for 14-3-3 binding. The expression of 14-3-3zeta increases phosphocofilin levels, and the coexpression of 14-3-3zeta with LIMK further elevates phosphocofilin levels and potentiates LIMK-dependent effects on the actin cytoskeleton. This potentiation of cofilin action appears to be a result of the protection of phosphocofilin from phosphatase-mediated dephosphorylation at Ser3 by bound 14-3-3zeta. Taken together, these results suggest that 14-3-3zeta proteins may play a dynamic role in the regulation of cellular actin structures through the maintenance of phosphocofilin levels.

Publication types

  • Research Support, Non-U.S. Gov't
  • Research Support, U.S. Gov't, P.H.S.

MeSH terms

  • 14-3-3 Proteins
  • Actin Depolymerizing Factors
  • Actins / metabolism*
  • Animals
  • Binding Sites
  • Cattle
  • Cytoskeleton / chemistry
  • Cytoskeleton / metabolism
  • Humans
  • Mass Spectrometry
  • Microfilament Proteins / chemistry*
  • Microfilament Proteins / metabolism*
  • Phosphorylation
  • Phosphoserine / metabolism
  • Protein Binding
  • Tyrosine 3-Monooxygenase / metabolism*


  • 14-3-3 Proteins
  • Actin Depolymerizing Factors
  • Actins
  • Microfilament Proteins
  • Phosphoserine
  • Tyrosine 3-Monooxygenase