Regulatory domain selectivity in the cell-type specific PKN-dependence of cell migration

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...

Full description

Saved in:
Bibliographic Details
Published in:PloS one 2011-07, Vol.6 (7), p.e21732-e21732
Main Authors: Lachmann, Sylvie, Jevons, Amy, De Rycker, Manu, Casamassima, Adele, Radtke, Simone, Collazos, Alejandra, Parker, Peter J
Format: Article
Language:English
Subjects:
Amino Acid Sequence
Analysis
Animals
Biology
Bladder
Bladder cancer
Cattle
Cell adhesion & migration
Cell Line, Tumor
Cell migration
Cell Movement
Cytoskeleton
Drosophila
G proteins
Gene expression
Gene Knockdown Techniques
Humans
Insects
Isoenzymes - chemistry
Isoenzymes - metabolism
Isoforms
Kinases
Laboratories
Medicine
Molecular Sequence Data
Morphogenesis
Neoplasm Invasiveness
Organ Specificity
Phosphorylation
Prostate
Prostate cancer
Protein kinase
Protein Kinase C - chemistry
Protein Kinase C - metabolism
Protein kinases
Protein Structure, Tertiary
Proteins
Redundancy
Regulators
Selectivity
Serine
Threonine
Tumors
Urinary bladder
Urinary Bladder Neoplasms - enzymology
Urinary Bladder Neoplasms - genetics
Urinary Bladder Neoplasms - pathology
Wound Healing
Citations: Items that this one cites
Items that cite this one
Online Access:Get full text
Tags: Add Tag
No Tags, Be the first to tag this record!
Description
Summary: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.
ISSN:1932-6203
1932-6203
DOI:10.1371/journal.pone.0021732