title: Regulatory domain selectivity in the cell-type specific PKN-dependence of cell migration.
abstract: The mammalian protein kinase N (PKN) family of Serine/Threonine kinases comprises three isoforms, which are targets for Rho family GTPases. Small GTPases are major regulators of the cellular cytoskeleton, generating interest in the role(s) of specific PKN isoforms in processes such as cell migration and invasion. It has been reported that PKN3 is required for prostate tumour cell invasion but not PKN1 or 2. Here we employ a cell model, the 5637 bladder tumour cell line where PKN2 is relatively highly expressed, to assess the potential redundancy of these isoforms in migratory responses. It is established that PKN2 has a critical role in the migration and invasion of these cells. Furthermore, using a PKN wild-type and chimera rescue strategy, it is shown that PKN isoforms are not simply redundant in supporting migration, but appear to be linked through isoform specific regulatory domain properties to selective upstream signals. It is concluded that intervention in PKNs may need to be directed at multiple isoforms to be effective in different cell types.
authors.affiliation: Protein Phosphorylation Laboratory, London Research Institute, London, United Kingdom.
authors.forename: Sylvie
authors.initials: S
authors.lastname: Lachmann
authors.forename: Amy
authors.initials: A
authors.lastname: Jevons
authors.forename: Manu
authors.initials: M
authors.lastname: De Rycker
authors.forename: Adele
authors.initials: A
authors.lastname: Casamassima
authors.forename: Simone
authors.initials: S
authors.lastname: Radtke
authors.forename: Alejandra
authors.initials: A
authors.lastname: Collazos
authors.forename: Peter J
authors.initials: PJ
authors.lastname: Parker
mesh_terms: D000595:Amino Acid Sequence; D000818:Animals; D002417:Cattle; D045744:Cell Line, Tumor; D002465:Cell Movement; D055785:Gene Knockdown Techniques; D006801:Humans; D007527:Isoenzymes / Q000737:chemistry / Q000378:metabolism; D008969:Molecular Sequence Data; D009361:Neoplasm Invasiveness; D009928:Organ Specificity; D011493:Protein Kinase C / Q000737:chemistry* / Q000378:metabolism*; D017434:Protein Structure, Tertiary; D001749:Urinary Bladder Neoplasms / Q000201:enzymology / Q000235:genetics / Q000473:pathology; D014945:Wound Healing
chemical_list: D007527:Isoenzymes; C061570:protein kinase N; D011493:Protein Kinase C