Zhan Yu, Chadee Deborah N
Department of Biological Sciences; University of Toledo; Toledo, OH USA.
Small GTPases. 2010 Nov;1(3):183-186. doi: 10.4161/sgtp.1.3.14935.
Mammalian mitogen-activated protein kinase (MAPK) signaling pathways respond to diverse extracellular signals and coordinate a range of cellular responses. Mixed lineage kinase 3 (MLK3) is a member of the mixed lineage kinase family of MAPK kinase kinases (MAP3Ks) that functions to regulate multiple MAPK signaling pathways. Activated forms of the Rho GTP ases, Rac and Cdc42, interact with MLK3 through the Cdc42/Rac-interactive binding (CRIB) motif and promote MLK3 catalytic activity. Our recent findings demonstrate that merlin, the product of the neurofibromatosis type 2 (NF2) tumor suppressor gene, is a physiological inhibitor of MLK3. Our results suggest that merlin inhibits MLK3 activity by blocking the Cdc42-MLK3 interaction. In this commentary, the effect of merlin on Cdc42-mediated activation of MLK3 and MAPK signaling will be discussed.
哺乳动物的丝裂原活化蛋白激酶（MAPK）信号通路可对多种细胞外信号作出反应，并协调一系列细胞反应。混合谱系激酶3（MLK3）是MAPK激酶激酶（MAP3Ks）混合谱系激酶家族的成员，其作用是调节多个MAPK信号通路。Rho GTP酶的活化形式Rac和Cdc42通过Cdc42/Rac相互作用结合（CRIB）基序与MLK3相互作用，并促进MLK3的催化活性。我们最近的研究结果表明，神经纤维瘤病2型（NF2）肿瘤抑制基因的产物默林（merlin）是MLK3的生理抑制剂。我们的结果表明，默林通过阻断Cdc42与MLK3的相互作用来抑制MLK3的活性。在这篇评论中，将讨论默林对Cdc42介导的MLK3激活和MAPK信号传导的影响。
