cGMP-dependent protein kinase I is involved in neurite outgrowth via a Rho effector, rhotekin, in Neuro2A neuroblastoma cells

Biochem Biophys Res Commun. 2012 May 4;421(2):239-44. doi: 10.1016/j.bbrc.2012.03.143. Epub 2012 Apr 4.

Abstract

Although the cGMP/cGMP-dependent protein kinase (cGK) signaling is involved in the regulation of neurite outgrowth, its mechanism remains to be clarified. In this study, we identified a Rho effector, rhotekin, as a cGK-I-interacting protein. Rhotekin was also a substrate for cGK-Iα. In neurite-extended Neuro2A neuroblastoma cells, cGK-Iα and rhotekin were colocalized in the plasma membrane and extended neurites, while treatment with cGMP resulted in translocation of rhotekin to the cytoplasm. In addition, we found that cGK-Iα and rhotekin synergistically suppressed Rho-induced neurite retraction. Our findings suggest that cGK-Iα interacts with and phosphorylates rhotekin, thereby contributing to neurite outgrowth regulation.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Animals
  • Apoptosis Regulatory Proteins
  • Cell Line, Tumor
  • Cyclic GMP-Dependent Protein Kinase Type I
  • Cyclic GMP-Dependent Protein Kinases / metabolism*
  • GTP-Binding Proteins
  • Intracellular Signaling Peptides and Proteins / genetics
  • Intracellular Signaling Peptides and Proteins / metabolism*
  • Mice
  • Neurites / physiology*
  • Phosphorylation
  • Serine / genetics
  • Serine / metabolism

Substances

  • Apoptosis Regulatory Proteins
  • Intracellular Signaling Peptides and Proteins
  • Rtkn protein, mouse
  • Serine
  • Cyclic GMP-Dependent Protein Kinase Type I
  • Cyclic GMP-Dependent Protein Kinases
  • Prkg1 protein, mouse
  • GTP-Binding Proteins