Map2k4δ - Identification and functional characterization of a novel Map2k4 splice variant
Map2k4δ - Identification and functional characterization of a novel Map2k4 splice variant
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DOI：
10.1016/j.bbamcr.2014.01.028
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发表时间：
2014-05-01
影响因子：
5.1
通讯作者：
Waetzig, Vicki
中科院分区：
文献类型：
--
作者：
Haeusgen, Wiebke;Tueffers, Leif;Waetzig, Vicki
丝裂原活化蛋白激酶激酶4（Map 2k 4）是双特异性丝氨酸/苏氨酸蛋白激酶，其在所有MAP 2K中在活化丝裂原活化蛋白激酶的两个不同亚家族（c-Jun N-末端激酶（JNK）和p38激酶）中是独特的。Map 2k 4在胚胎发生过程中是必不可少的，并参与多种生理和病理过程。然而，关于其在癌症发展中作用的研究揭示了部分相互矛盾的数据。在本研究中，我们报告了一种新的剪接变体Map 2k 4，Map 2k 4三角洲，与一个额外的外显子在前面的底物结合D-结构域的鉴定。Map 2k 4 δ与Map 2k 4一起在大鼠、小鼠和人的各种组织中表达。在PC 12细胞中，这两种剪接变体通过使用不同的信号通路控制细胞周期进程和基础凋亡。如果Map 2k 4和Map 2k 4 δ的表达和活化处于特定的细胞类型特异性平衡，则确保适当的细胞生长。一种激酶的过表达破坏了复杂的平衡，导致高度增殖或促凋亡表型，部分反映了文献中关于Map 2k 4及其在肿瘤发展中的作用的差异。我们的研究结果有助于理解以前的研究，并指出Map 2k 4并不总是具有明确的功能，而是与其他调节剂一起触发细胞反应。(c)2014 Elsevier B. V.保留所有权利。
Mitogen-activated protein kinase kinase 4 (Map2k4) is a dual specificity serin/threonine protein kinase that is unique among all MAP2Ks in activating two different subfamilies of mitogen-activated protein kinases, the c-Jun N-terminal kinases (JNKs) and p38 kinases. Map2k4 is essential during embryogenesis and involved in a variety of physiological and pathological processes. However, studies on its role in cancer development revealed partially conflicting data. In the present study, we report the identification of a novel splice variant of Map2k4, Map2k4 delta, with an additional exon in front of the substrate binding D-domain. Map2k4 delta is expressed together with Map2k4 in various tissues from rat, mouse and human. In PC12 cells, both splice variants control cell cycle progression and basal apoptosis by using different signaling pathways. If expression and activation of Map2k4 and Map2k4 delta are at a certain, cell type-specific equilibrium, an appropriate cell growth is ensured. Overexpression of one kinase disrupts the intricate balance and either results in a highly proliferative or pro-apoptotic phenotype, partially reflecting the discrepancies in the literature on Map2k4 and its role in tumor development. Our findings contribute to the understanding of previous studies and point out that Map2k4 has not always a definite function, but rather triggers a cellular reaction in concert with other modulators. (c) 2014 Elsevier B.V. All rights, reserved.