Map2k4未 鈥?Identification and functional characterization of a novel Map2k4 splice variant

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• 作者：Wiebke Haeusgen ; Leif Tueffers ; Thomas Herdegen ; Vicki Waetzig ; ^{vicki.waetzig@pharmakologie.uni-kiel.de" class="auth_mail}
• 关键词：AKT ; protein kinase B ; ATF-2 ; activating transcription factor 2 ; BrdU ; 5-bromo-2-deoxyuridine ; DVD ; domain of versatile docking ; E ; embryonic day ; ERK ; extracellular signal-regulated kinase ; Fas-L ; Fas ligand ; ID ; immunodepletion ; IP ; immunoprecipitation ; JNK ; c-Jun N-terminal kinase ; MAPK ; mitogen-activated protein kinase ; MAP2K/MKK ; mitogen-activated protein kinase kinase ; MAP3K ; mitogen-activated protein kinase kinase kinase ; Mdm-2 ; mouse double minute 2 homolog ; MEF ; mouse embryonic fibrobla
• 刊名：Biochimica et Biophysica Acta (BBA)/Molecular Cell Research
• 出版年：May, 2014
• 年：2014
• 卷：1843
• 期：5
• 页码：875-884
• 全文大小：1180 K

文摘

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未, with an additional exon in front of the substrate binding D-domain. Map2k4未 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未 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.