title: Effect of cancer-associated mutations in the PlexinB1 gene.
abstract: BACKGROUND
  Semaphorins act as chemotactic cues for cell movement via their transmembrane receptors, plexins. Somatic missense mutations in the plexinB1 gene coupled with overexpression of the protein frequently occur in prostate tumours, indicating a role for plexinB1 in the pathogenesis of prostate cancer.
  
  
  RESULTS
  Two specific mutations found in prostate cancer enhance RhoD binding and one other mutation results in loss of inhibition of Rac-dependent Pak1 phosphorylation and lamellipodia formation and in impairment of trafficking of plexinB1 to the membrane. None of the three characterised mutations affect PDZRhoGEF binding, RhoA activity, the interaction of plexinB1 with the oncogenes ErbB2 or c-Met or ErbB2 phosphorylation. The mutations have the net effect of increasing cell motility by blocking plexinB1-mediated inhibition of Rac while enhancing the interaction with RhoD, an anti-migratory factor.
  
  
  CONCLUSIONS
  PlexinB1 mutations block plexinB1-mediated signalling pathways that inhibit cell motility.
authors.affiliation: Prostate Cancer Research Centre, University College London, 67, Riding House Street, London W1W 7EJ, UK.
authors.forename: Chun
authors.initials: C
authors.lastname: Zhou
authors.forename: Oscar Gee-Wan
authors.initials: OG
authors.lastname: Wong
authors.forename: John R
authors.initials: JR
authors.lastname: Masters
authors.forename: Magali
authors.initials: M
authors.lastname: Williamson
mesh_terms: D000818:Animals; D002460:Cell Line; D002462:Cell Membrane / Q000378:metabolism; D002522:Chlorocebus aethiops; D004789:Enzyme Activation / Q000235:genetics; D006801:Humans; D008297:Male; D009154:Mutation; D009419:Nerve Tissue Proteins / Q000235:genetics*; D010766:Phosphorylation; D011471:Prostatic Neoplasms / Q000235:genetics* / Q000378:metabolism; D011485:Protein Binding; D021381:Protein Transport; D019859:Proto-Oncogene Proteins c-met / Q000378:metabolism; D018719:Erb-b2 Receptor Tyrosine Kinases / Q000378:metabolism; D011956:Receptors, Cell Surface / Q000235:genetics*; D015398:Signal Transduction; D054462:p21-Activated Kinases / Q000378:metabolism; D020744:rac GTP-Binding Proteins / Q000378:metabolism; D020741:rho GTP-Binding Proteins / Q000378:metabolism; D020742:rhoA GTP-Binding Protein / Q000378:metabolism
chemical_list: D009419:Nerve Tissue Proteins; D019859:Proto-Oncogene Proteins c-met; D018719:Erb-b2 Receptor Tyrosine Kinases; D011956:Receptors, Cell Surface; D054462:p21-Activated Kinases; D020744:rac GTP-Binding Proteins; D020741:rho GTP-Binding Proteins; D020742:rhoA GTP-Binding Protein; C492119:PLXNB1 protein, human; C515903:PAK1 protein, human; C105243:RHOD protein, human