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

TY - JOUR

T1 - Stress-activated protein kinase-3 interacts with the PDZ domain of α1- syntrophin

T2 - A mechanism for specific substrate recognition

AU - Hasegawa, Masato

AU - Cuenda, Ana

AU - Spillantini, Maria Grazia

AU - Thomas, Gareth M.

AU - Buée-Scherrer, Valérie

AU - Cohen, Philip

AU - Goedert, Michel

PY - 1999/4/30

Y1 - 1999/4/30

N2 - 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.

AB - 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.

UR - https://www.scopus.com/pages/publications/0033617341

U2 - 10.1074/jbc.274.18.12626

DO - 10.1074/jbc.274.18.12626

M3 - Article

C2 - 10212242

AN - SCOPUS:0033617341

SN - 0021-9258

VL - 274

SP - 12626

EP - 12631

JO - Journal of Biological Chemistry

JF - Journal of Biological Chemistry

IS - 18

ER -