ERK-8, a new member of the mitogen-activated protein kinase family
ERK-8, a new member of the mitogen-activated protein kinase family
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DOI：
10.1074/jbc.m112483200
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发表时间：
2002-05-10
影响因子：
4.8
通讯作者：
Rosner, MR
中科院分区：
文献类型：
--
作者：
Abe, MK;Saelzler, MP;Rosner, MR
ERK是与细胞生长和分化有关的MAPK的一个亚家族。通过使用大鼠ERK 7 cDNA筛选人类多组织cDNA文库，我们确定了ERK家族的新成员，ERK 8，与ERK 7共享69%的氨基酸序列同一性。北方分析表明ERK 8存在于许多组织中，在肺和肾中表达最大。荧光原位杂交定位ERK 8基因的染色体8，带q24.3。ERK 8在COS细胞和细菌中的表达表明，与组成型活性ERK 7相反，ERK 8具有最小的基础激酶活性和独特的底物谱。ERK 8在其C-末端区域含有两个SH 3结合基序，在体外与c-Src SH 3结构域相关联，并在体内与c-Src共免疫沉淀。与v-Src或组成型活性c-Src共转染增加ERK 8活化，表明ERK 8可以在c-Src下游被活化。ERK 8在血清刺激后也被激活，并且这种激活的程度通过用特异性Src家族抑制剂PP 2预处理而降低。血清或Src对ERK 8的激活不受MEK抑制剂U 0126的影响，表明ERK 8的激活不需要MEK 1、MEK 2或MEK 5。虽然与ERK 7最密切相关，但相对较低的序列同一性、最小的基础活性和不同的底物谱将ERK 8鉴定为由Src依赖性信号传导途径激活的MAPK家族的不同成员。
The ERKs are a subfamily of the MAPKs that have been implicated in cell growth and differentiation. By using the rat ERK7 cDNA to screen a human multiple tissue cDNA library, we identified a new member of the ERK family, ERK8, that shares 69% amino acid sequence identity with ERK7. Northern analysis demonstrates that ERK8 is present in a number of tissues with maximal expression in the lung and kidney. Fluorescence in situ hybridization localized the ERK8 gene to chromosome 8, band q24.3. Expression of ERK8 in COS cells and bacteria indicates that, in contrast to constitutively active ERK7, ERK8 has minimal basal kinase activity and a unique substrate profile. ERK8, which contains two SH3-binding motifs in its C-terminal region, associates with the c-Src SH3 domain in vitro and co-immunoprecipitates with c-Src in vivo. Co-transfection with either v-Src or a constitutively active c-Src increases ERK8 activation indicating that ERK8 can be activated downstream of c-Src. ERK8 is also activated following serum stimulation, and the extent of this activation is reduced by pretreatment with the specific Src family inhibitor PP2. The ERK8 activation by serum or Src was not affected by the MEK inhibitor U0126 indicating that activation of ERK8 does not require MEK1, MEK2, or MEK5. Although most closely related to ERK7, the relatively low sequence identity, minimal basal activity, and different substrate profile identify ERK8 as a distinct member of the MAPK family that is activated by an Src-dependent signaling pathway.