PTEN is a protein tyrosine phosphatase for IRS1 Journal Article
| Authors: | Shi, Y.; Wang, J.; Chandarlapaty, S.; Cross, J.; Thompson, C.; Rosen, N.; Jiang, X. |
| Article Title: | PTEN is a protein tyrosine phosphatase for IRS1 |
| Abstract: | The biological function of the PTEN tumor suppressor is mainly attributed to its lipid phosphatase activity. This study demonstrates that mammalian PTEN is a protein tyrosine phosphatase that selectively dephosphorylates insulin receptor substrate-1 (IRS1), a mediator of insulin and IGF signals. IGF signaling was defective in cells lacking NEDD4, a PTEN ubiquitin ligase, whereas AKT activation triggered by EGF or serum was unimpaired. Defective IGF signaling caused by NEDD4 deletion, including phosphorylation of IRS1 and AKT, was rescued by PTEN ablation. We demonstrate the nature of PTEN as an IRS1 phosphatase by direct biochemical analysis and cellular reconstitution, showing that NEDD4 supports insulin-mediated glucose metabolism and is required for the proliferation of IGF1 receptor-dependent but not EGF receptor-dependent tumor cells. Thus, PTEN is a protein phosphatase for IRS1, and its antagonism by NEDD4 promotes signaling by IGF and insulin. © 2014 Nature America, Inc. |
| Keywords: | signal transduction; epidermal growth factor; protein kinase b; somatomedin; human cell; pathophysiology; mammalia; ubiquitin protein ligase; lipid; obesity; rna interference; enzyme activity; enzyme phosphorylation; regulatory mechanism; diabetes mellitus; recombinant protein; western blotting; phosphatidylinositol 3,4,5 trisphosphate 3 phosphatase; insulin; glucose; protein tyrosine phosphatase; ubiquitin protein ligase nedd4; short hairpin rna; enzyme assay; dephosphorylation; glucose metabolism; insulin receptor substrate 1; human; priority journal; article; hek293 cell line; cell growth assay; phospholipid vesicle |
| Journal Title: | Nature Structural and Molecular Biology |
| Volume: | 21 |
| Issue: | 6 |
| ISSN: | 1545-9993 |
| Publisher: | Nature Publishing Group |
| Date Published: | 2014-06-01 |
| Start Page: | 522 |
| End Page: | 527 |
| Language: | English |
| DOI: | 10.1038/nsmb.2828 |
| PROVIDER: | scopus |
| PUBMED: | 24814346 |
| PMCID: | PMC4167033 |
| DOI/URL: | |
| Notes: | Nat. Struct. Mol. Biol. -- Export Date: 8 July 2014 -- CODEN: NSMBC -- Source: Scopus |
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