RRC ID 2048
Author Nagai-Tamai Y, Mizuno K, Hirose T, Suzuki A, Ohno S.
Title Regulated protein-protein interaction between aPKC and PAR-3 plays an essential role in the polarization of epithelial cells.
Journal Genes Cells
Abstract BACKGROUND:Recent studies have revealed that aPKC (atypical protein kinase C), PAR-3 and PAR-6 play indispensable roles in the regulation of various cell polarization events, from worms to mammals, suggesting that they comprise an evolutionarily conserved protein machinery which is essential for cell polarization. The three proteins interact with each other to form a ternary complex and thus mutually regulate their functionality and localization. Here, we investigated the biochemical nature of the aPKC-PAR-3 interaction in detail to clarify its functional importance in cell polarity.
RESULTS:The highly conserved 26 amino acid sequence 816-841, in PAR-3 was found to be necessary and sufficient for the tight association with aPKC. Among several conserved serine/threonine residues within the region, aPKC preferentially phosphorylates serine-827 in vitro, and this phosphorylation reduces the stability of the PAR-3-aPKC interaction. Several analyses using a phospho-serine 827 specific antibody have established that this phosphorylation by aPKC occurs in vivo. Over-expression of a point mutant of PAR-3 (S827A), which is predicted to form a stable complex with aPKC, causes defects in the cell-cell contact-induced cell polarization of epithelial MDCK cells, similarly to a dominant negative mutant of aPKC.
CONCLUSIONS:These results imply that serine 827 in the aPKC binding site of PAR-3 is a target of aPKC and that the regulated interaction between a protein kinase, aPKC, and its substrate, PAR-3, plays an essential role in the establishment of cell polarity.
Volume 7(11)
Pages 1161-71
Published 2002-11-1
DOI 10.1046/j.1365-2443.2002.00590.x
PII 590
PMID 12390250
MeSH Amino Acid Substitution Animals Binding Sites Caenorhabditis elegans / genetics Caenorhabditis elegans / metabolism Caenorhabditis elegans Proteins / genetics Caenorhabditis elegans Proteins / metabolism* Conserved Sequence In Vitro Techniques Phosphorylation Point Mutation Protein Binding / genetics Protein Binding / physiology Protein Kinase C / genetics Protein Kinase C / metabolism* Protein Serine-Threonine Kinases
IF 1.655
Times Cited 124
DNA material AxCALacZ (RDB01745)