ISOLATION OF MEK5 AND DIFFERENTIAL EXPRESSION OF ALTERNATIVELY SPLICED FORMS
ISOLATION OF MEK5 AND DIFFERENTIAL EXPRESSION OF ALTERNATIVELY SPLICED FORMS
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DOI：
10.1074/jbc.270.48.28897
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发表时间：
1995-12-01
影响因子：
4.8
通讯作者：
COBB, MH
中科院分区：
文献类型：
--
作者：
ENGLISH, JM;VANDERBILT, CA;COBB, MH
原型丝裂原活化蛋白（MAP）激酶模块是一个由MAP激酶、细胞外信号调节蛋白激酶（ERK） 1或ERK2、MAP/ERK激酶（MEK） MEK1或MEK2以及MEK激酶Raf-1或B-Raf组成的三激酶级联。这种和其他MAP激酶模块被认为是主要细胞事件的关键信号转导器，包括增殖、分化和应激反应。为了鉴定新的哺乳动物MAP激酶模块，采用聚合酶链反应从大鼠中分离出新的MEK家族成员MEK5。与其他已知的哺乳动物MEKs， MKK3和MKK4相比，MEK5与MEK1和MEK2的关系更为密切。MEK5被认为位于一个未表征的MAP激酶通路中，因为MEK5不会使ERK/MAP激酶家族成员ERK1、ERK2、ERK3、JNK/SAPK或p38/HOG1磷酸化，也不会使Raf-1、c-Mos或MEKK1高度磷酸化。选择性剪接导致MEK5的50 kda α和40 kda β亚型。MEK5 β无处不在，主要分布在细胞质中。MEK5 α在肝脏和大脑中表达最高，呈颗粒状。在较大的α同型中，由5'外显子编码的23个氨基酸与某些被认为与肌动蛋白细胞骨架相关的蛋白质中的序列相似；这种选择性拼接的模块结构域可能导致MEK5 α的差异亚细胞定位。
The prototype mitogen-activated protein (MAP) kinase module is a three-kinase cascade consisting of the MAP kinase, extracellular signal-regulated protein kinase (ERK) 1 or ERK2, the MAP/ERK kinase (MEK) MEK1 or MEK2, and the MEK kinase, Raf-1 or B-Raf. This and other MAP kinase modules are thought to be critical signal transducers in major cellular events including proliferation, differentiation, and stress responses. To identify novel mammalian MAP kinase modules, polymerase chain reaction was used to isolate a new MEK family member, MEK5, from the rat. MEK5 is more closely related to MEK1 and MEK2 than to the other known mammalian MEKs, MKK3 and MKK4. MEK5 is thought to lie in an uncharacterized MAP kinase pathway, because MEK5 does not phosphorylate the ERK/MAP kinase family members ERK1, ERK2, ERK3, JNK/SAPK, or p38/HOG1, nor will Raf-1, c-Mos, or MEKK1 highly phosphorylate it. Alternative splicing results in a 50-kDa alpha and a 40-kDa beta isoform of MEK5. MEK5 beta is ubiquitously distributed and primarily cytosolic. MEK5 alpha is expressed most highly in liver and brain and is particulate. The 23 amino acids encoded by the 5' exon in the larger alpha isoform are similar to a sequence found in certain proteins believed to associate with the actin cytoskeleton; this alternatively spliced modular domain may lead to the differential subcellular localization of MEK5 alpha.