MAPKAP kinase 2 phosphorylates serum response factor in vitro and in vivo

J Biol Chem. 1999 May 14;274(20):14434-43. doi: 10.1074/jbc.274.20.14434.

Abstract

Several growth factor- and calcium-regulated kinases such as pp90(rsk) or CaM kinase IV can phosphorylate the transcription factor serum response factor (SRF) at serine 103 (Ser-103). However, it is unknown whether stress-regulated kinases can also phosphorylate SRF. We show that treatment of cells with anisomycin, arsenite, sodium fluoride, or tetrafluoroaluminate induces phosphorylation of SRF at Ser-103 in both HeLa and NIH3T3 cells. This phosphorylation is dependent on the kinase p38/SAPK2 and correlates with the activation of MAPKAP kinase 2 (MK2). MK2 phosphorylates SRF in vitro at Ser-103 with similar efficiency as the small heat shock protein Hsp25 and significantly better than CREB. Comparison of wild type murine fibroblasts with those derived from MK2-deficient mice (Mk(-/-)) reveals MK2 as the major SRF kinase induced by arsenite. These results demonstrate that SRF is targeted by several signal transduction pathways within cells and establishes SRF as a nuclear target for MAPKAP kinase 2.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • 3T3 Cells
  • Animals
  • Arsenites / pharmacology
  • Calcium-Calmodulin-Dependent Protein Kinases / metabolism
  • DNA-Binding Proteins / metabolism*
  • Fibroblasts / drug effects
  • Fibroblasts / metabolism
  • HeLa Cells
  • Humans
  • Intracellular Signaling Peptides and Proteins
  • Mice
  • Mitogen-Activated Protein Kinases*
  • Nuclear Proteins / metabolism*
  • Phosphorylation
  • Protein-Serine-Threonine Kinases / metabolism*
  • Serine / metabolism
  • Serum Response Factor
  • Signal Transduction / drug effects
  • Teratogens / pharmacology
  • p38 Mitogen-Activated Protein Kinases

Substances

  • Arsenites
  • DNA-Binding Proteins
  • Intracellular Signaling Peptides and Proteins
  • Nuclear Proteins
  • Serum Response Factor
  • Teratogens
  • Serine
  • MAP-kinase-activated kinase 2
  • Protein-Serine-Threonine Kinases
  • Calcium-Calmodulin-Dependent Protein Kinases
  • Mitogen-Activated Protein Kinases
  • p38 Mitogen-Activated Protein Kinases
  • arsenite