Regulation of PTEN stability and activity by Plk3 Journal Article

Authors: Xu, D.; Yao, Y.; Jiang, X.; Lu, L.; Dai, W.
Article Title: Regulation of PTEN stability and activity by Plk3
Abstract: By studying primary isogenic murine embryonic fibroblasts (MEFs), we have shown that PLK3 null MEFs contain a reduced level of phosphatase and tensin homolog (PTEN) and increased Akt1 activation coupled with decreased GSK3β activation under normoxia and hypoxia. Purified recombinant Plk3, but not a kinase-defective mutant, efficiently phosphorylates PTEN in vitro. Mass spectrometry identifies threonine 366 and serine 370 as two putative residues that are phosphorylated by Plk3. Immunoblotting using a phosphospecific antibody confirms these sites as Plk3 phosphorylation sites. Moreover, treatment of MEFs with LiCl, an inhibitor of GSK3β and CK2, only partially suppresses the phosphorylation, suggesting Plk3 as an additional kinase that phosphorylates these sites in vivo. Plk3-targeting mutants of PTEN are expressed at a reduced level in comparison with the wild-type counterpart, which is associated with an enhanced activity of PDK1, an upstream activator of Akt1. Furthermore, the reduced level of PTEN in PLK3 null MEFs is stabilized by treatment with MG132, a proteosome inhibitor. Combined, our study identifies Plk3 as a new player in the regulation of the PI3K/PDK1/Akt signaling axis by phosphorylation and stabilization of PTEN. © 2010 by The American Society for Biochemistry and Molecular Biology, Inc.
Keywords: signal transduction; protein kinase b; controlled study; human cell; mutation; nonhuman; mass spectrometry; animal cell; mouse; animals; mice; mice, knockout; serine; embryo; in vivo study; enzyme activation; in vitro study; enzyme activity; cysteine proteinase inhibitors; phosphorylation; wild type; phosphatidylinositol 3 kinase; enzyme phosphorylation; cell culture; protein-serine-threonine kinases; glycogen synthase kinase 3beta; phosphatidylinositol 3,4,5 trisphosphate 3 phosphatase; proto-oncogene proteins c-akt; pten phosphohydrolase; wild types; murinae; immunoblotting; fibroblast; fibroblasts; embryo, mammalian; in-vivo; threonine; amino acids; adjuvants, immunologic; in-vitro; mutant; phosphoinositide dependent protein kinase 1; glycogen synthase kinase 3; chemical activation; enzyme stability; hek293 cells; leupeptins; murine embryonic fibroblasts; phosphorylation sites; phosphospecific antibodies; polo like kinase 3; lithium chloride
Journal Title: Journal of Biological Chemistry
Volume: 285
Issue: 51
ISSN: 0021-9258
Publisher: American Society for Biochemistry and Molecular Biology  
Date Published: 2010-12-17
Start Page: 39935
End Page: 39942
Language: English
DOI: 10.1074/jbc.M110.166462
PUBMED: 20940307
PROVIDER: scopus
PMCID: PMC3000975
Notes: --- - "Export Date: 20 April 2011" - "CODEN: JBCHA" - "Source: Scopus"
Citation Impact
MSK Authors
  1. Xuejun Jiang
    102 Jiang