Amiloride inhibits the protein tyrosine kinases associated with the cellular and the transforming src-gene products.
Amiloride inhibits a protein tyrosine kinase from rat brain extracts. The kinase activity is characterized by an anti-serum (TBR-serum) which immunoprecipitates pp60c-src, the cellular counterpart of the transforming protein pp60v-src of Rous sarcoma virus. In immunocomplexes, TBR-IgG serves as an artificial but specific phosphate acceptor. The phosphate incorporation into TBR-IgG is a time- and temperature-dependent process. In the presence of amiloride the TBR-IgG phosphorylation is reduced. The drug does not influence the immunocomplexes formed by TBR-IgG and pp60src and no amiloride-activated protein tyrosine phosphatase can be detected in the immunocomplex system. Half-maximal inhibition of the tyrosine kinase occurs at 300 microM amiloride and is competitive with respect to ATP. Viral pp60src kinase of transformed cells is more sensitive to amiloride (IC50: 50-100 microM). Furthermore, normal cellular tyrosine kinases are to a lesser extent inhibited by amiloride as compared to the transforming viral pp60src kinase. These results may indicate different amiloride-sensitive forms of cellular pp60src kinases.
D000255:Adenosine Triphosphate / Q000378:metabolism; D000584:Amiloride / Q000494:pharmacology*; D000818:Animals; D000936:Antigen-Antibody Complex / Q000378:metabolism; D001358:Avian Sarcoma Viruses / Q000201:enzymology; D001921:Brain / Q000201:enzymology; D007074:Immunoglobulin G / Q000378:metabolism; D015688:Oncogene Protein pp60(v-src); D011505:Protein-Tyrosine Kinases / Q000037:antagonists & inhibitors*; D011518:Proto-Oncogene Proteins / Q000037:antagonists & inhibitors*; D016392:Proto-Oncogene Proteins pp60(c-src); D051381:Rats; D011919:Rats, Inbred Strains; D012191:Retroviridae Proteins / Q000037:antagonists & inhibitors*
D000936:Antigen-Antibody Complex; D007074:Immunoglobulin G; D011518:Proto-Oncogene Proteins; D012191:Retroviridae Proteins; D000584:Amiloride; D000255:Adenosine Triphosphate; D011505:Protein-Tyrosine Kinases; D015688:Oncogene Protein pp60(v-src); D016392:Proto-Oncogene Proteins pp60(c-src)