Aurandt Jennifer, Li Weiquan, Guan Kun-Liang
Life Sciences Institute, University of Michigan, Ann Arbor, MI 48109, USA.
Biochem J. 2006 Mar 1;394(Pt 2):459-64. doi: 10.1042/BJ20051123.
Semaphorins are a large family of transmembrane and secreted proteins that signal primarily through the receptor plexin. Semaphorins have been characterized in the nervous system as axon guidance cues; however, they have also been shown to control development of other cellular systems such as the vasculature and lungs. As the role of semaphorins outside of the nervous system has broadened, so has elucidation of the intracellular signalling pathways they initiate. Previously, we and others have shown that plexin-B1 activates RhoA through the binding and activation of RhoGEF (guanine nucleotide-exchange factor)/LARG (leukaemia-associated RhoGEF) in response to semaphorin 4D stimulation. In the present study, we show that semaphorin 4D activates the MAPK (mitogen-activated protein kinase) pathway. We have found that the mechanism of activation requires the C-terminus of plexin-B1 and the activation of RhoA.
信号素是一大类跨膜和分泌蛋白，主要通过受体丛蛋白发出信号。信号素在神经系统中作为轴突导向因子已得到充分研究；然而，它们也被证明可控制其他细胞系统的发育，如脉管系统和肺。随着信号素在神经系统外作用的不断扩展，对其启动的细胞内信号通路的阐明也不断深入。此前，我们和其他研究人员已表明，在信号素4D刺激下，丛蛋白-B1通过结合并激活RhoGEF（鸟嘌呤核苷酸交换因子）/LARG（白血病相关RhoGEF）来激活RhoA。在本研究中，我们发现信号素4D激活丝裂原活化蛋白激酶（MAPK）通路。我们发现，激活机制需要丛蛋白-B1的C末端以及RhoA的激活。
