The London Research Institute hosts a number of conferences throughout the year and has extensive seminar schedules as part of its education programme.
Highlighted Paper: Regulatory Domain Selectivity in the Cell-Type Specific PKN-Dependence of Cell Migration
Submitted by goodwi02 on Thu, 01/09/2011 - 09:35
The Protein Phosphorylation Lab headed by Peter Parker published this paper in PLoS One.
Lachmann S, Jevons A, De Rycker M, Casamassima A, Radtke S, Collazos A, Parker PJ. Regulatory Domain Selectivity in the Cell-Type Specific PKN-Dependence of Cell Migration. PLoS One. 2011;6(7):e21732
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The overarching question underlying this study concerned the general engagement of members of the PKN serine/threonine protein kinase family in migration and invasion. Prior evidence had indicated that, related to its up-regulation in advanced prostate cancer, PKN3 and not the related PKN1 or PKN2 family members, played an essential role in the invasive behaviour of a prostate cancer cell model. Our initial work directed more broadly at the role of these protein kinases in migratory and invasive behaviour of tumour cells led us to the conclusion that PKN1 and PKN2 also contribute to the regulation of migration/invasion and that the distinction with the prostate model was likely a feature of the cell model.
We went on to demonstrate that the requirement for PKNs was not simply a function of the pattern of expression of family members, indicating a degree of non-redundancy and suggestive of either kinase specificity or regulatory-specific inputs determining cell-type specific requirements. Establishing stable cell lines expressing chimeric proteins in a bladder model normally dependent on PKN2 for migration (see Figure), we demonstrated through knock-down and rescue that it was the regulatory domain of PKN2 that confers this specific dependence. The implication is that the regulatory network that promotes migration and invasion is differentially wired in diverse cells to engage distinct members of the PKN family and that by contrast the output from these protein kinases may be conserved. It is further concluded that intervention in this family of proteins as a means of suppressing metastatic disease might be most effective if targeting all three members.
