Stress-activated protein kinase-3 interacts with the PDZ domain of α1-syntrophin -: A mechanism for specific substrate recognition
Stress-activated protein kinase-3 interacts with the PDZ domain of α1-syntrophin -: A mechanism for specific substrate recognition
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DOI：
10.1074/jbc.274.18.12626
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发表时间：
1999-04-30
影响因子：
4.8
通讯作者：
Goedert, M
中科院分区：
文献类型：
--
作者：
Hasegawa, M;Cuenda, A;Goedert, M
选择性靶向独特亚细胞位点的机制在决定蛋白激酶的底物特异性方面起着重要作用。（SAPK3，也称为ERK 6和p38 γ），其是在骨骼肌中大量表达的促分裂原活化蛋白激酶家族的成员，通过其羧基末端序列-KETXL与α 1-促突触蛋白的PDZ结构域结合，SAPK3磷酸化α 1-在体外，促突触蛋白在丝氨酸残基193和201处磷酸化，并且磷酸化依赖于α 1-促突触蛋白的PDZ结构域的结合，在骨骼肌中，SAPK3和α 1-突触营养蛋白共定位于神经肌肉接头处，并且这两种蛋白质可以从转染的COS细胞裂解物中共免疫沉淀，PDZ结构域的磷酸化-结合蛋白激酶对蛋白质的抑制作用是一种新的确定蛋白激酶定位和底物特异性的机制。
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 p38 gamma), 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 alpha 1-syntrophin, SAPK3 phosphorylates alpha 1-syntrophin at serine residues 193 and 201 in vitro and phosphorylation is dependent on binding 60 the PDZ domain of alpha 1-syntrophin, In skeletal muscle SAPK3 and alpha 1-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.