The p85beta regulatory subunit of PI3K serves as a substrate for PTEN protein phosphatase activity during insulin mediated signaling.
Phosphatase and tensin homolog deleted on chromosome 10 (PTEN) is a tumor suppressor gene that is frequently mutated in brain, uterine, and prostate cancers. The protein phosphatase activity is poorly defined. We demonstrate that insulin stimulates phosphorylation of tyrosine and threonine/proline residues on the p85 regulatory subunit of PI3K in Huh-7, and HEK 293 cells. The specificity of PTEN binding and dephosphorylation of PI3K appears to reside on the p85beta subunit. Therefore, the PTEN phosphatase is active against the PI3K p85beta subunit and dephosphorylates a protein involved in insulin signaling where known downstream consequences are increased cell migration, motility, and invasion.
Liver Research Center, Warren Alpert Medical School of Brown University, Providence, RI 02913, United States.
Jiman
J
He
Suzanne
S
de la Monte
Jack R
JR
Wands
D020134:Catalytic Domain / Q000235:genetics; D002460:Cell Line; D006801:Humans; D007328:Insulin / Q000378:metabolism* / Q000494:pharmacology; D009154:Mutation; D051059:PTEN Phosphohydrolase / Q000235:genetics / Q000378:metabolism*; D019869:Phosphatidylinositol 3-Kinases / Q000378:metabolism*; D010766:Phosphorylation; D011392:Proline / Q000378:metabolism; D021122:Protein Subunits / Q000378:metabolism; D051057:Proto-Oncogene Proteins c-akt / Q000819:agonists / Q000037:antagonists & inhibitors / Q000378:metabolism; D015398:Signal Transduction; D013912:Threonine / Q000378:metabolism; D014443:Tyrosine / Q000378:metabolism
D007328:Insulin; D021122:Protein Subunits; D013912:Threonine; D014443:Tyrosine; D011392:Proline; D019869:Phosphatidylinositol 3-Kinases; D051057:Proto-Oncogene Proteins c-akt; D051059:PTEN Phosphohydrolase