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 NIH 3T3 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.