Fig. 2. Sema4D uses two different receptors. Sema4D is a member of the class IV semaphorin subfamily. Several consensus sites for serine phosphorylation exist in the cytoplasmic domain. Although Sema4D is a transmembrane-type semaphorin, it can be proteolytically cleaved from the surface to produce a soluble form. Serine kinase activities associated with the cytoplasmic region of Sema4D are implicating in the regulation of Sema4D proteolytic cleavage. Sema4D uses two receptors, CD72 and plexin-B1. Sema4D exerts its effects on immune cells, such as B cells and DCs, through CD72, whereas it induces growth cone collapse and epithelial cell invasive growth through plexin-B1 and plexin-B1/Met, respectively. Of note, the extracellular region of plexin-B1 is also cleaved (Artigiani et al., 2003).