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标题：Protein phosphatase 1 regulates the phosphorylation state of the polarity scaffold Par-3
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作者：Andreas Traweger ; Giselle Wiggin ; Lorne Taylor 等
期刊名称：Proceedings of the National Academy of Sciences
印刷版ISSN：0027-8424
电子版ISSN：1091-6490
出版年度：2008
卷号：105
期号：30
页码：10402-10407
DOI：10.1073/pnas.0804102105
语种：English
出版社：The National Academy of Sciences of the United States of America
摘要：Phosphorylation of the polarity protein Par-3 by the serine/threonine kinases aPKC{zeta}/{iota} and Par-1 (EMK1/MARK2) regulates various aspects of epithelial cell polarity, but little is known about the mechanisms by which these posttranslational modifications are reversed. We find that the serine/threonine protein phosphatase PP1 (predominantly the isoform) binds Par-3, which localizes to tight junctions in MDCKII cells. PP1 can associate with multiple sites on Par-3 while retaining its phosphatase activity. By using a quantitative mass spectrometry-based technique, multiple reaction monitoring, we show that PP1 specifically dephosphorylates Ser-144 and Ser-824 of mouse Par-3, as well as a peptide encompassing Ser-885. Consistent with these observations, PP1 regulates the binding of 14-3-3 proteins and the atypical protein kinase C (aPKC) {zeta} to Par-3. Furthermore, the induced expression of a catalytically inactive mutant of PP1 severely delays the formation of functional tight junctions in MDCKII cells. Collectively, these results show that Par-3 functions as a scaffold, coordinating both serine/threonine kinases and the PP1 phosphatase, thereby providing dynamic control of the phosphorylation events that regulate the Par-3/aPKC complex.
关键词：epithelial polarity ; multiple reaction monitoring ; tight junctions ; phosphorylation dynamics