Sema4D induces angiogenesis through Met recruitment by Plexin B1.
Semaphorins, a large family of membrane-bound and secreted proteins, signal through their transmembrane receptors, the plexins. Semaphorins and plexins share structural homologies with scatter factor receptors, a family of tyrosine kinase receptors for which Met is the prototype. Semaphorins have been studied primarily in the developing nervous system, where they act as repelling cues in axon guidance. However, they are widely expressed in several tissues, and their role in epithelial morphogenesis has been recently established. Not much is known about their role in angiogenesis, a key step during embryonic development and adulthood. Here we demonstrate that a semaphorin, Sema4D, is angiogenic in vitro and in vivo and that this effect is mediated by its high-affinity receptor, Plexin B1. Moreover, we prove that biologic effects elicited by Plexin B1 require coupling and activation of the Met tyrosine kinase. In sum, we identify a proangiogenic semaphorin and provide insight about the signaling machinery exploited by Plexin B1 to control angiogenesis.
Conrotto
Paolo
P
Division of Molecular Oncology, Department of Oncological Sciences, IRCC, Institute for Cancer Research and Treatment, University of Torino School of Medicine, Strada Provinciale 142 10060, Candiolo, Torino, Italy.
Valdembri
Donatella
D
Corso
Simona
S
Serini
Guido
G
Tamagnone
Luca
L
Comoglio
Paolo Maria
PM
Bussolino
Federico
F
Giordano
Silvia
S
D000818:Animals; D015703:Antigens, CD / Q000502:physiology*; D049109:Cell Proliferation; D002478:Cells, Cultured; D002642:Chick Embryo; D004730:Endothelium, Vascular / Q000166:cytology*; D006801:Humans; D051379:Mice; D018919:Neovascularization, Physiologic; D009419:Nerve Tissue Proteins / Q000378:metabolism / Q000502:physiology*; D011518:Proto-Oncogene Proteins / Q000378:metabolism*; D019859:Proto-Oncogene Proteins c-met; D020794:Receptor Protein-Tyrosine Kinases / Q000502:physiology; D011956:Receptors, Cell Surface / Q000378:metabolism / Q000502:physiology*; D017978:Receptors, Growth Factor / Q000378:metabolism*; D039961:Semaphorins / Q000502:physiology*; D015398:Signal Transduction
D015703:Antigens, CD; C093224:CD100 antigen; D009419:Nerve Tissue Proteins; C492119:PLXNB1 protein, human; D011518:Proto-Oncogene Proteins; D011956:Receptors, Cell Surface; D017978:Receptors, Growth Factor; D039961:Semaphorins; C491743:MET protein, human; D019859:Proto-Oncogene Proteins c-met; D020794:Receptor Protein-Tyrosine Kinases