Stress-activated protein kinase-3 interacts with the PDZ domain of alpha1-syntrophin. A mechanism for specific substrate recognition

J Biol Chem. 1999 Apr 30;274(18):12626-31. doi: 10.1074/jbc.274.18.12626.


Mechanisms for selective targeting to unique subcellular sites play an important role in determining the substrate specificities of protein kinases. Here we show that stress-activated protein kinase-3 (SAPK3, also called ERK6 and p38gamma), a member of the mitogen-activated protein kinase family that is abundantly expressed in skeletal muscle, binds through its carboxyl-terminal sequence -KETXL to the PDZ domain of alpha1-syntrophin. SAPK3 phosphorylates alpha1-syntrophin at serine residues 193 and 201 in vitro and phosphorylation is dependent on binding to the PDZ domain of alpha1-syntrophin. In skeletal muscle SAPK3 and alpha1-syntrophin co-localize at the neuromuscular junction, and both proteins can be co-immunoprecipitated from transfected COS cell lysates. Phosphorylation of a PDZ domain-containing protein by an associated protein kinase is a novel mechanism for determining both the localization and the substrate specificity of a protein kinase.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Amino Acid Sequence
  • Animals
  • Bungarotoxins / metabolism
  • COS Cells
  • Calcium-Binding Proteins
  • Fluorescent Antibody Technique
  • Membrane Proteins / chemistry
  • Membrane Proteins / metabolism*
  • Mitogen-Activated Protein Kinase 12
  • Mitogen-Activated Protein Kinases*
  • Molecular Sequence Data
  • Muscle Proteins / chemistry
  • Muscle Proteins / metabolism*
  • Muscle, Skeletal / enzymology
  • Muscle, Skeletal / metabolism
  • Neuromuscular Junction / enzymology
  • Neuromuscular Junction / metabolism
  • Peptide Fragments / chemistry
  • Peptide Fragments / metabolism
  • Phosphorylation
  • Precipitin Tests
  • Protein Binding
  • Protein Kinases / metabolism*
  • Rats
  • Rats, Sprague-Dawley
  • Substrate Specificity


  • Bungarotoxins
  • Calcium-Binding Proteins
  • Membrane Proteins
  • Muscle Proteins
  • Peptide Fragments
  • syntrophin alpha1
  • Protein Kinases
  • Mitogen-Activated Protein Kinase 12
  • Mitogen-Activated Protein Kinases