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

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.
Mesh Terms:
Amino Acid Sequence, Animals, Bungarotoxins, COS Cells, Calcium-Binding Proteins, Fluorescent Antibody Technique, Membrane Proteins, Mitogen-Activated Protein Kinase 12, Mitogen-Activated Protein Kinases, Molecular Sequence Data, Muscle Proteins, Muscle, Skeletal, Neuromuscular Junction, Peptide Fragments, Phosphorylation, Precipitin Tests, Protein Binding, Protein Kinases, Rats, Rats, Sprague-Dawley, Substrate Specificity
J. Biol. Chem.
Date: Apr. 30, 1999
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