Atypical PKC Phosphorylates PAR-1 Kinases to Regulate Localization and Activity
2004; Elsevier BV; Volume: 14; Issue: 8 Linguagem: Inglês
10.1016/j.cub.2004.04.007
ISSN1879-0445
AutoresJonathan Hurov, Janis L. Watkins, Helen Piwnica‐Worms,
Tópico(s)Microtubule and mitosis dynamics
ResumoThe establishment and maintenance of cellular polarity are essential biological processes that must be maintained throughout the lifetime of eukaryotic organisms. The Par-1 protein kinases are key polarity determinants that have been conserved throughout evolution. Par-1 directs anterior-posterior asymmetry in the one-cell C. elegans embryo and the Drosophila oocyte [1Pellettieri J Seydoux G Anterior-posterior polarity in C. elegans and Drosophila–PARallels and differences.Science. 2002; 298: 1946-1950Crossref PubMed Scopus (105) Google Scholar]. In mammalian cells, Par-1 may regulate epithelial cell polarity [2Bohm H Brinkman V Drab M Henske A Kurzchalia T.V Mammalian Homologues of C-elegans polarization gene product PAR-1 are asymmetrically localized in epithelial cells and may influence their polarity.Curr. Biol. 1997; 7: 603-606Abstract Full Text Full Text PDF PubMed Google Scholar]. Relevant substrates of Par-1 in these pathways are just being identified, but it is not yet known how Par-1 itself is regulated. Here, we demonstrate that human Par-1b (hPar-1b) interacts with and is negatively regulated by atypical PKC. hPar-1b is phosphorylated by aPKC on threonine 595, a residue conserved in Par-1 orthologs in mammals, worms, and flies. The equivalent site in hPar-1a, T564, is phosphorylated in vivo and by aPKC in vitro. Importantly, phosphorylation of hPar-1b on T595 negatively regulates the kinase activity and plasma membrane localization of hPar-1b in vivo. This study establishes a novel functional link between two central determinants of cellular polarity, aPKC and Par-1, and suggests a model by which aPKC may regulate Par-1 in polarized cells.
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