Association of inhibition of cell growth by O-phospho-L-tyrosine with decreased tyrosine phosphorylation.
We have previously demonstrated that O-phospho-L-tyrosine (P-Tyr), a substrate for a wide range of PTPases, inhibits the growth of human renal cell carcinoma and human breast cancer cell lines and suppresses EGF-mediated EGFR tyrosine phosphorylation. We now show that P-Tyr inhibited the growth of the human hepatoma cell line HEPG2, and src transformed NIH3T3 cells, but did not inhibit the growth of human ovarian carcinoma SKOV-3 cells. Addition of exogenous P-Tyr inhibited the insulin triggered insulin receptor (IR) tyrosine phosphorylation in the HEPG2 cell line and the tyrosine phosphorylation of a variety of cellular proteins in src-transformed NIH3T3 cells. P-Tyr did not inhibit the tyrosine phosphorylation of gp185 erbB-2 in P-Tyr resistant SKOV-3 cells. Thus, inhibition of cell growth by P-tyr was associated with decreased tyrosine phosphorylation of cellular proteins.
Mishra
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University of Maryland Cancer Center; Department of Pathology, Baltimore, 21201, USA.
Hamburger
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AW
D016475:3T3 Cells / Q000166:cytology / Q000187:drug effects; D000818:Animals; D000970:Antineoplastic Agents / Q000494:pharmacology*; D006528:Carcinoma, Hepatocellular / Q000188:drug therapy / Q000378:metabolism; D002455:Cell Division / Q000187:drug effects / Q000502:physiology; D004347:Drug Interactions; D005260:Female; D006801:Humans; D007328:Insulin / Q000494:pharmacology; D008113:Liver Neoplasms / Q000188:drug therapy / Q000378:metabolism; D051379:Mice; D009363:Neoplasm Proteins / Q000378:metabolism*; D009369:Neoplasms / Q000188:drug therapy / Q000378:metabolism*; D010051:Ovarian Neoplasms / Q000188:drug therapy / Q000378:metabolism; D010766:Phosphorylation / Q000187:drug effects; D019000:Phosphotyrosine / Q000494:pharmacology*; D016392:Proto-Oncogene Proteins pp60(c-src) / Q000378:metabolism; D018719:Erb-b2 Receptor Tyrosine Kinases / Q000378:metabolism; D011972:Receptor, Insulin / Q000378:metabolism; D014407:Tumor Cells, Cultured; D014443:Tyrosine / Q000378:metabolism*
D000970:Antineoplastic Agents; D007328:Insulin; D009363:Neoplasm Proteins; D019000:Phosphotyrosine; D016392:Proto-Oncogene Proteins pp60(c-src); D018719:Erb-b2 Receptor Tyrosine Kinases; D011972:Receptor, Insulin; D014443:Tyrosine