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PMID: 19635806 Published · ppublish English Journal Article Research Support, Non-U.S. Gov't

p85 Associates with unphosphorylated PTEN and the PTEN-associated complex.

Molecular and cellular biology ·Vol. 29 ·No. 19 ·2009-10-00 ·Pages 5377-88

Rabinovsky R, Pochanard P, McNear C, Brachmann SM, Duke-Cohan JS, Garraway LA, Sellers WR

Abstract

The lipid phosphatase PTEN functions as a tumor suppressor by dephosphorylating the D3 position of phosphoinositide-3,4,5-trisphosphate, thereby negatively regulating the phosphoinositide 3-kinase (PI3K)/AKT signaling pathway. In mammalian cells, PTEN exists either as a monomer or as a part of a >600-kDa complex (the PTEN-associated complex [PAC]). Previous studies suggest that the antagonism of PI3K/AKT signaling by PTEN may be mediated by a nonphosphorylated form of the protein resident within the multiprotein complex. Here we show that PTEN associates with p85, the regulatory subunit of PI3K. Using newly generated antibodies, we demonstrate that this PTEN-p85 association involves the unphosphorylated form of PTEN engaged within the PAC and also includes the p110beta isoform of PI3K. The PTEN-p85 association is enhanced by trastuzumab treatment and linked to a decline in AKT phosphorylation in some ERBB2-amplified breast cancer cell lines. Together, these results suggest that integration of p85 into the PAC may provide a novel means of downregulating the PI3K/AKT pathway.

MeSH Terms
Amino Acid Sequence Antibodies/immunology Cell Line Humans Molecular Sequence Data Molecular Weight PTEN Phosphohydrolase/chemistry,genetics,immunology,metabolism Phosphatidylinositol 3-Kinases/metabolism Phosphorylation Protein Binding Protein Subunits/metabolism Receptor, ErbB-2/immunology
Chemicals
Antibodies Protein Subunits Phosphatidylinositol 3-Kinases Receptor, ErbB-2 PTEN Phosphohydrolase PTEN protein, human
Authors & Affiliations
7 authors, click to expand affiliations / ORCID
Rabinovsky Rosalia
Department of Medical Oncology, Dana-Farber Cancer Institute, 44 Binney St., Boston, MA 02115, USA.
Pochanard Panisa
McNear Chontelle
Brachmann Saskia M
Duke-Cohan Jonathan S
Garraway Levi A
Sellers William R
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Article Info
Journal
Molecular and cellular biology
Abbr.
Mol Cell Biol
ISSN
1098-5549
DOI
10.1128/MCB.01649-08
Published
2009-10-00
Epub
2009-00-27
Pages
5377-88
Language
English
Region
United States
NLM ID
8109087
PMCID
PMC2747981
Subset
IM
Grants
NCI NIH HHS · R01 CA085912 · United States
External Links
PubMed source DOI: 10.1128/MCB.01649-08 PMC Full Text View journal details
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