Plexins with

The presence of PDZ (PSD-95/SAP90-Discs-larg-ZO-l) domains in the RhoGEFs predicted their likely association with other proteins. Several groups identified plexin B as a target through two-hybrid analysis with... 

Subsequent studies have identified Rndl (Oinuma et al, 2003), another member of the Rho GTPase subfamily, and the ErbB-2 tyrosine kinase (Swiercz et al, 2004) in the regulation of RhoA by plexins. Additionally, an apparent requirement for interaction of plexin B with RhoGEFs for potentiation of angiogenesis by semaphorins (Basile et al., 2004) and activation of MAPK pathways (Aurandt et al, 2006) by plexin Bl was identified. Yet, direct evidence for the mechanism by which plexins achieve this activation of RhoA has been elusive. A simple mechanism would be localization of the RhoGEF to membranes on stimulation of the pathway as discussed in Section III.B. Evidence for this comes from a study (Oinuma et al, 2003) with Rndl, which can bind directly to plexin Bl. 

Aurandt, J., Vikis, H. G., Gutkind, J. S., Ahn, N., and Guan, K. L. (2002). The semaphorin receptor plexin-Bl signals through a direct interaction with the Rho-specific nucleotide exchange factor, LARG. Proc. Natl. Acad. Sci. USA 99, 12085-12090. 

Hirotani, M., Ohoka, Y., Yamamoto, T., Nirasawa, H., Furuyama, T., Kogo, M., Matsuya, T., and Inagaki, S. (2002). Interaction of plexin-Bl with PDZ domain-containing Rho guanine nucleotide exchange factors. Biochem. Biophys. Res. Com-mun. 297, 32-37. 

Oinuma, I., Katoh, H., Harada, A., and Negishi, M. (2003). Direct interaction of Rndl with Plexin-Bl regulates PDZ-RhoGEF-mediated Rho activation by Plexin-Bl and induces cell contraction in COS-7 cells. J. Biol. Chem. 278, 25671-25677. 

Swiercz, J. M., Kuner, R., Behrens, J., and Offermanns, S. (2002). Plexin-Bl directly interacts with PDZ-RhoGEF/LARG to regulate RhoA and growth cone morphology. 

Vertebrate A-Plexins are the signaling subunits for secreted class 3 semaphorins, while other plexins interact with semaphorins from different classes (Fiore and Piischel, 2003). In contrast to SemaSA, which is not able to bind directly to A-Plexins, SemalD and Sema7A directly interact with Plexin-Bl and Plexin-Cl, respectively (Takahashi et al, 1999 Tamagnone et al, 1999). Interestingly, all Plexins contain an extracellular semaphorin domain that is strictly required for their function (Fig. 7). A semaphorin domain is also present in the scatter-factor receptor MET (Tamagnone et al, 1999). 

Plxndl Plexin D1 expressed in pulmonary vasculature—significantly associated with phosgene survival... 

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