Cofilin phosphorylation and actin polymerization by NRK/NESK, a member of the germinal center kinase family

Exp Cell Res. 2003 Jul 15;287(2):219-27. doi: 10.1016/s0014-4827(03)00136-8.

Abstract

Nck-interacting kinase (NIK)-related kinase (NRK)/NIK-like embryo-specific kinase (NESK) is a protein kinase that belongs to the germinal center kinase family, and activates the c-Jun N-terminal kinase (JNK) signaling pathway. In this study, we examined the effect of NRK/NESK on actin cytoskeletal organization. Overexpression of NRK/NESK in COS7 cells induced accumulation of polymerized actin at the perinuclear. Phosphorylation of cofilin, an actin-depolymerizing factor, was increased in NRK/NESK-expressing HEK 293T cells. In addition, in vitro phosphorylation of cofilin was observed on NRK/NESK immunoprecipitates from HEK 293T cells expressing the kinase domain of NRK/NESK. The cofilin phosphorylation occurred at the serine residue of position 3 (Ser-3). Since the phosphorylation at Ser-3 inactivates the actin-depolymerizing activity of cofilin, these results suggest that NRK/NESK induces actin polymerization through cofilin phosphorylation. The cofilin phosphorylation did not appear to be mediated through activation of LIM-kinasel, a cofilin-phosphorylating kinase, or through the activation of JNK. Thus, cofilin is likely to be a direct substrate of NRK/NESK. NRK/NESK is predominantly expressed in skeletal muscle during the late stages of mouse embryogenesis. Thus, NRK/NESK may be involved in the regulation of actin cytoskeletal organization in skeletal muscle cells through cofilin phosphorylation.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Actin Depolymerizing Factors
  • Actins / metabolism*
  • Animals
  • Biopolymers / metabolism
  • COS Cells
  • Cell Line
  • Chlorocebus aethiops
  • Germinal Center / metabolism
  • Germinal Center Kinases
  • Intracellular Signaling Peptides and Proteins
  • Microfilament Proteins / metabolism*
  • Phosphorylation
  • Protein Kinases / chemistry
  • Protein Kinases / metabolism*
  • Protein Structure, Tertiary
  • Protein-Serine-Threonine Kinases / chemistry
  • Protein-Serine-Threonine Kinases / metabolism*
  • Serine / metabolism

Substances

  • Actin Depolymerizing Factors
  • Actins
  • Biopolymers
  • Germinal Center Kinases
  • Intracellular Signaling Peptides and Proteins
  • Microfilament Proteins
  • Serine
  • Protein Kinases
  • Nik related kinase
  • Protein-Serine-Threonine Kinases