Stress-activated protein kinase-3 interacts with the PDZ domain of α1- syntrophin: A mechanism for specific substrate recognition

Masato Hasegawa, Ana Cuenda, Maria Grazia Spillantini, Gareth M. Thomas, Valérie Buée-Scherrer, Philip Cohen, Michel Goedert

    Research output: Contribution to journalArticlepeer-review

    138 Citations (Scopus)

    Abstract

    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 p38γ), 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 α1-syntrophin. SAPK3 phosphorylates α1-syntrophin at serine residues 193 and 201 in vitro and phosphorylation is dependent on binding to the PDZ domain of α1-syntrophin. In skeletal muscle SAPK3 and α1-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.

    Original languageEnglish
    Pages (from-to)12626-12631
    Number of pages6
    JournalJournal of Biological Chemistry
    Volume274
    Issue number18
    DOIs
    Publication statusPublished - 30 Apr 1999

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