Semaphorin 4D activates the MAPK pathway downstream of plexin-B1.
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.
Aurandt
Jennifer
J
Life Sciences Institute, University of Michigan, Ann Arbor, MI 48109, USA.
Li
Weiquan
W
Guan
Kun-Liang
KL
D000818:Animals; D015703:Antigens, CD / Q000378:metabolism*; D002460:Cell Line; D002462:Cell Membrane / Q000378:metabolism; D004789:Enzyme Activation; D006801:Humans; D020935:MAP Kinase Signaling System; D051379:Mice; D020929:Mitogen-Activated Protein Kinase Kinases / Q000378:metabolism*; D009419:Nerve Tissue Proteins / Q000737:chemistry / Q000235:genetics / Q000378:metabolism*; D010766:Phosphorylation; D011956:Receptors, Cell Surface / Q000737:chemistry / Q000235:genetics / Q000378:metabolism*; D039961:Semaphorins / Q000378:metabolism*; D018631:ras Proteins / Q000378:metabolism; D020741:rho GTP-Binding Proteins / Q000378:metabolism
D015703:Antigens, CD; C093224:CD100 antigen; D009419:Nerve Tissue Proteins; C492119:PLXNB1 protein, human; D011956:Receptors, Cell Surface; D039961:Semaphorins; D020929:Mitogen-Activated Protein Kinase Kinases; D018631:ras Proteins; D020741:rho GTP-Binding Proteins