ASSOCIATION OF INHIBITION OF CELL-GROWTH BY O-PHOSPHO-L-TYROSINE WITHDECREASED TYROSINE PHOSPHORYLATION

We have previously demonstrated that O-phospho-L-tyrosine (P-Tyr), a s ubstrate for a wide range of PTPases, inhibits the growth of human ren al cell carcinoma and human breast cancer cell lines and suppresses EG F-mediated EGFR tyrosine phosphorylation. We now show that P-TYr inhib ited the growth of the human hepatoma cell line HEPG2, and src transfo rmed NIH 3T3 cells, but did not inhibit the growth of human ovarian ca rcinoma SKOV-3 cells. Addition of exogenous P-5r inhibited the insulin triggered insulin receptor (IR) tyrosine phosphorylation in the HEPG2 cell line and !he tyrosine phosphorylation of a variety of cellular p roteins in src-transformed NIH3T3 cells. P-5r did not inhibit the tyro sine phosphorylation of gp(185) erbB-2 in P-5r resistant SKOV-3 cells. Thus, inhibition of cell growth by P-tyr was associated with decrease d tyrosine phosphorylation of cellular proteins.