Activation of the Sap-1a transcription factor by the c-Jun N-terminal kinase (JNK) mitogen-activated protein kinase

J Biol Chem. 1997 Feb 14;272(7):4219-24. doi: 10.1074/jbc.272.7.4219.

Abstract

Ternary complex factors (TCFs) bind to the serum response element in the c-fos promoter and mediate its activation by many extracellular stimuli. Some of these stimuli activate the ERK subclass of mitogen-activated protein kinases (MAPKs) that target the TCF Sap-1a. We show that Sap-1a is also phosphorylated by the stress-activated JNK subclass of MAPKs leading to stimulation of both c-fos serum response element and E74-site-dependent transcription in RK13 cells. Several JNK-1 phosphorylation sites were mapped within Sap-1a, and mutation of these sites affected the transactivation mediated by Sap-1a and JNK-1. The impact of these phosphorylation sites varied at different promoters and was dependent on whether Sap-1a was stimulated by ERK-1 or JNK-1. Additionally, a comparison of Sap-1a with another TCF, Elk-1, revealed that these proteins behaved differently to stimulation by ERK-1 and JNK-1. Furthermore, activation of Sap-1a by JNK-1 was inhibited by the p38(MAPK) in RK13 cells, possibly by competition for a common upstream activator. Altogether, our data suggest that Sap-1a plays an important role in the nuclear response elicited by cellular stress.

Publication types

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

MeSH terms

  • Animals
  • Calcium-Calmodulin-Dependent Protein Kinases / metabolism
  • Cells, Cultured
  • DNA-Binding Proteins / genetics
  • DNA-Binding Proteins / metabolism*
  • JNK Mitogen-Activated Protein Kinases*
  • MAP Kinase Kinase 4
  • Mitogen-Activated Protein Kinase Kinases*
  • Mitogen-Activated Protein Kinases*
  • Mutagenesis, Site-Directed
  • Phosphorylation
  • Protein Kinase Inhibitors
  • Protein Kinases / metabolism*
  • Rabbits
  • Transcription Factors / genetics
  • Transcription Factors / metabolism*
  • ets-Domain Protein Elk-4
  • p38 Mitogen-Activated Protein Kinases

Substances

  • DNA-Binding Proteins
  • Protein Kinase Inhibitors
  • Transcription Factors
  • ets-Domain Protein Elk-4
  • Protein Kinases
  • Calcium-Calmodulin-Dependent Protein Kinases
  • JNK Mitogen-Activated Protein Kinases
  • Mitogen-Activated Protein Kinases
  • p38 Mitogen-Activated Protein Kinases
  • MAP Kinase Kinase 4
  • Mitogen-Activated Protein Kinase Kinases