SKK4, a novel activator of stress-activated protein kinase-1 (SAPK1/JNK)

FEBS Lett. 1997 Sep 1;414(1):153-8. doi: 10.1016/s0014-5793(97)00990-3.

Abstract

A cDNA was cloned and expressed that encodes human stress-activated protein kinase kinase-4 (SKK4), a novel MAP kinase kinase family member whose mRNA is widely expressed in human tissues. SKK4 activated SAPK1/JNK in vitro, but not SAPK2a/p38, SAPK2b/p38beta, SAPK3/ERK6 or SAPK4. It appears to be the mammalian homologue of HEP, an activator of SAPK1/JNK in Drosophila. In human epithelial KB cells SKK4 and SKK1/MKK4 (another activator of SAPK1/JNK) were both activated by stressful stimuli, but only SKK4 was activated by proinflammatory cytokines. The identification of SKK4 explains why the major SAPK1/JNK activator detected in many mammalian cell extracts is chromatographically separable from SKK1/MKK4.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Amino Acid Sequence
  • Animals
  • Base Sequence
  • Calcium-Calmodulin-Dependent Protein Kinases / metabolism*
  • Cloning, Molecular
  • Cytokines / pharmacology
  • Enzyme Activation
  • Escherichia coli
  • Humans
  • Interleukin-1 / pharmacology
  • JNK Mitogen-Activated Protein Kinases
  • KB Cells
  • MAP Kinase Kinase 4*
  • MAP Kinase Kinase 7
  • Mitogen-Activated Protein Kinase 12
  • Mitogen-Activated Protein Kinase Kinases*
  • Mitogen-Activated Protein Kinases*
  • Molecular Sequence Data
  • Protein Kinases / metabolism
  • Protein Serine-Threonine Kinases / chemistry
  • Protein Serine-Threonine Kinases / genetics
  • Protein Serine-Threonine Kinases / metabolism*
  • Protein-Tyrosine Kinases / metabolism
  • Recombinant Fusion Proteins / metabolism
  • Sequence Analysis, DNA
  • Sequence Homology, Amino Acid
  • Substrate Specificity
  • Tumor Necrosis Factor-alpha / pharmacology
  • p38 Mitogen-Activated Protein Kinases

Substances

  • Cytokines
  • Interleukin-1
  • Recombinant Fusion Proteins
  • Tumor Necrosis Factor-alpha
  • Protein Kinases
  • Mitogen-Activated Protein Kinase 12
  • Protein-Tyrosine Kinases
  • Protein Serine-Threonine Kinases
  • Calcium-Calmodulin-Dependent Protein Kinases
  • JNK Mitogen-Activated Protein Kinases
  • Mitogen-Activated Protein Kinases
  • p38 Mitogen-Activated Protein Kinases
  • MAP Kinase Kinase 4
  • MAP Kinase Kinase 7
  • MAP2K4 protein, human
  • MAP2K7 protein, human
  • Mitogen-Activated Protein Kinase Kinases

Associated data

  • GENBANK/H85962