Plexins

Plexins comprise a family of transmembrane proteins that serve as receptors for semaphorins. On the basis... 

Both plexins and semaphorins are structurally characterized by the presence of an extracellular sema domain which contains a seven-blade 3-propeller. The... 

Plexins. Table 1 Plexins and their respective semaphorin ligands... 

Semaphorins and plexins were first described to be involved in the guidance of axonal growth cones during... 

The semaphorin-plexin system has been shown to be involved both in tumour suppression and tumour progression. The genes encoding Sema3B and Sema3F... 

Negishi M, Oinuma I, Katoh H (2005) Plexins axon guidance and signal transduction. Cell Mol Life Sci 62 1363-1371... 

The Sema domain consisting of about 500 amino acids is characterized by highly conserved cysteine residues that form intramolecular disulfide bonds. Crystal structures have revealed that the Sema domain folds in the manner of the (3 propeller topology which is also found in integrins or the low-density lipoprotein (LDL) receptors. Sema domains are found in semaphorins, plexins and in the receptor tyrosine kinases Met and Ron. 

Semaphorins are secreted, membrane-associated or transmembrane proteins defined by the presence of a sema-phorin protein domain (Serna domain). In the mammalian system, more than 20 semaphorins have been identified which play important roles in a variety of tissues. The best characterized receptors for mediating semaphoiin effects are members of the neuropilin and plexin families of transmembrane proteins. Semaphoiin functions are best described in the regulation of neural development, angiogenesis, immunoregulation and cancer. 

Platinum Complexes Pleckstrin Homology Domain Plexins PMF... 

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. 

Identification of ErbB-2 tyrosine kinase in plexin B1 signaling suggests a potential role for phosphorylation (Swiercz et al., 2004). Semaphorin 4D stimulates phosphorylation of both the kinase and plexin Bl. This raises the interesting possibility that the PDZ-RhoGEFs could also be targets of the kinase and that phosphorylation would facilitate their activation as discussed in the previous section. The activation mechanism remains to be determined but could also include tonic stimulation by the G12- or G13 proteins. 

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