The online version of this article (doi:10.1186/1476-4598-11-11) contains supplementary material, which is available to authorized users.
Chun Zhou, Oscar Gee-Wan Wong contributed equally to this work.
A patent has been filed by M.W. and J.R.M. for mutations.
CZ and OW carried out the molecular genetic studies. JM participated in its design and coordination. MW conceived of the study, coordinated it and drafted the manuscript. All authors read and approved the final manuscript.
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.
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 plexinB1with 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.
PlexinB1 mutations block plexinB1-mediated signalling pathways that inhibit cell motility.
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- Effect of cancer-associated mutations in the PlexinB1 gene
Oscar Gee-Wan Wong
John R Masters
- BioMed Central
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