Semaphorin-4D (Sema4D, CD100) is a member of class 4 membrane-bound Semaphorins, which repels the
Quizartinib of hippocampal and retinal ganglion neurons in the developing nervous system [1] and [2]. Plexin-B1 is a neuronal Sema4D receptor and commands at least two different intracellular signaling [2]. One is the regulation of small G-proteins [2]. Plexin-B1 directly binds to Rac and competes with p21 activated kinase [3]. Plexin-B1 acts as GTPase activating protein for R-Ras [4]. Another small G-protein RhoA is also activated by the complex of Plexin-B1 and Rho-GEF proteins [1] and [5]. The other signaling conducted by Plexin-B1 is tyrosine
phosphorylation [6]. The binding of Sema4D to Plexin-B1 activates tyrosine kinases in which Plexin-B1 forms a hetero-complex with either one of receptor tyrosine kinases, c-Met or ErbB2 [7] and [8]. Sema4D also induces tyrosine-dephosphorylation of focal adhesion kinase in the cell lines expressing Plexin-B1 [9]. However, the molecular mechanism and biological significance of tyrosine-dephosphorylation in Sema4D-signaling have yet to be determined.
