Molecular cloning and characterization of a novel dual specificity phosphatase, MKP-5
Molecular cloning and characterization of a novel dual specificity phosphatase, MKP-5
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DOI：
10.1074/jbc.274.28.19949
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发表时间：
1999-07-09
影响因子：
4.8
通讯作者：
Nishida, E
中科院分区：
文献类型：
--
作者：
Tanoue, T;Moriguchi, T;Nishida, E
一组双特异性蛋白磷酸酶负调控丝裂原活化蛋白激酶（MAPK）超家族的成员，该超家族由三个主要亚家族组成，MAPK/细胞外信号调节激酶（ERK）、应激活化蛋白激酶（SAPK）/c-Jun N-末端激酶（JNK）和p38。这组双特异性磷酸酶的9个成员先前已被克隆。他们表现出不同的底物特异性的MAPK，不同的组织分布和亚细胞定位，和不同的模式诱导其表达的细胞外刺激。本研究克隆并鉴定了一种新的双特异性磷酸酶，命名为MKP-5。MKP-5由482个氨基酸组成，分子量为52.6kDa，N端由150个功能未知的氨基酸组成，中间有两个Cdc 25同源区，C端有一个催化结构域。MKP-5与p38和SAPK/JNK结合，但不与MAPK/ERK结合，并使p38和SAPK/JNK失活，但不使MAPK/ERK失活。p38是优选的底物。MKP-5的亚细胞定位是独特的;它均匀地存在于细胞质和细胞核中。MKP-5 mRNA在各种组织和器官中广泛表达，其在培养细胞中的表达因应激刺激而升高。这些结果表明，MKP-5是一种新型的p38和SAPK/JNK双特异性磷酸酶。
A group of dual specificity protein phosphatases negatively regulates members of the mitogen-activated protein kinase (MAPK) superfamily, which consists of three major subfamilies, MAPK/extracellular signal-regulated kinase (ERK), stress-activated protein kinase (SAPK)/c-Jun N-terminal kinase (JNK), and p38. Nine members of this group of dual specificity phosphatases have previously been cloned. They show distinct substrate specificities for MAPKs, different tissue distribution and subcellular localization, and different modes of inducibility of their expression by extracellular stimuli. Here we have cloned and characterized a novel dual specificity phosphatase, which we have designated MKP-5, MKP-5 is a protein of 482 amino acids with a calculated molecular mass of 52.6 kDa and consists of 150 N-terminal amino acids of unknown function, two Cdc25 homology 2 regions in the middle, and a C-terminal catalytic domain. MKP-5 binds to p38 and SAPK/JNK, but not to MAPK/ERK, and inactivates p38 and SAPK/JNK, but not MAPK/ERK. p38 is a preferred substrate, The subcellular localization of MKP-5 is unique; it is present evenly in both the cytoplasm and the nucleus. MKP-5 mRNA is widely expressed in various tissues and organs, and its expression in cultured cells is elevated by stress stimuli. These results suggest that MKP-5 is a novel type of dual specificity phosphatase specific for p38 and SAPK/JNK.