O-phospho-L-tyrosine inhibits cellular growth by activating protein tyrosine phosphatases.
O-Phospho-L-tyrosine (P-Tyr), a substrate for a wide range of protein tyrosine phosphatases, inhibited growth of human renal and breast carcinoma cells. Growth was blocked in the S phase of the cell cycle. A decrease in the amount of cyclin proteins A and B was also observed. P-Tyr incubation led to activation of cellular protein tyrosine phosphatases resulting in the inhibition of tyrosine phosphorylation of epidermal growth factor receptor as well as of p34cdc2. P-Tyr synergistically sensitized the renal carcinoma ACHN cells to killing by the chemotherapeutic agents doxorubicin and etoposide. These growth inhibitory properties of P-Tyr in vitro suggest its possible use as an anticancer agent.
Mishra
S
S
Department of Pathology, University of Maryland Cancer Center, Baltimore 21201.
Hamburger
A W
AW
D001943:Breast Neoplasms / Q000188:drug therapy / Q000201:enzymology / Q000473:pathology; D002292:Carcinoma, Renal Cell / Q000188:drug therapy / Q000201:enzymology / Q000473:pathology; D016923:Cell Death / Q000187:drug effects; D002455:Cell Division / Q000187:drug effects; D004317:Doxorubicin / Q000494:pharmacology; D004789:Enzyme Activation / Q000187:drug effects; D004815:Epidermal Growth Factor / Q000494:pharmacology; D066246:ErbB Receptors / Q000378:metabolism; D005047:Etoposide / Q000494:pharmacology; D006801:Humans; D007680:Kidney Neoplasms / Q000188:drug therapy / Q000201:enzymology / Q000473:pathology; D009363:Neoplasm Proteins / Q000378:metabolism; D010766:Phosphorylation; D019000:Phosphotyrosine; D017027:Protein Tyrosine Phosphatases / Q000187:drug effects / Q000378:metabolism*; D016196:S Phase / Q000187:drug effects; D012680:Sensitivity and Specificity; D014407:Tumor Cells, Cultured / Q000187:drug effects; D014443:Tyrosine / Q000031:analogs & derivatives* / Q000378:metabolism / Q000494:pharmacology
D009363:Neoplasm Proteins; D019000:Phosphotyrosine; D014443:Tyrosine; D004815:Epidermal Growth Factor; D005047:Etoposide; D004317:Doxorubicin; D066246:ErbB Receptors; D017027:Protein Tyrosine Phosphatases