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.