Stress-activated protein kinase-3 interacts with the PDZ domain of alpha 1-syntrophin - A mechanism for specific substrate recognition

Mechanisms for selective targeting to unique subcellular sites play an impo rtant role in determining the substrate specificities of protein kinases, H ere we show that stress-activated protein kinase-3 (SAPK3, also called ERK6 and p38 gamma), a member of the mitogen-activated protein kinase family th at is abundantly expressed in skeletal muscle, binds through its carboxyl-t erminal sequence -KETXL to the PDZ domain of alpha 1-syntrophin, SAPK3 phos phorylates alpha 1-syntrophin at serine residues 193 and 201 in vitro and p hosphorylation is dependent on binding 60 the PDZ domain of alpha 1-syntrop hin, In skeletal muscle SAPK3 and alpha 1-syntrophin co-localize at the neu romuscular junction, and both proteins can be co-immunoprecipitated from tr ansfected COS cell lysates, Phosphorylation of a PDZ domain-containing prot ein by an associated protein kinase is a novel mechanism for determining bo th the localization and the substrate specificity of a protein kinase.