P1,P4-Di(adenosine-5')tetraphosphate inhibits phosphorylation of immunoglobulin G by Rous sarcoma virus pp60src.
Di(adenosine-5')oligophosphate nucleotides of general structure ApnA (n = 2-6) inhibited phosphorylation of immunoglobulin G from tumor-bearing rabbits (TBR IgG) by pp60src protein kinase purified from Rous sarcoma virus-transformed rat tumor cells. Ap4A, a nucleotide associated with eukaryotic cell proliferation, was one of the most effective inhibitors in the series, causing 50% inhibition of TBR IgG phosphorylation at 15 microM. Ap4A inhibited pp60src-dependent phosphorylation of TBR IgG in solution and immunoprecipitates, as well as the phosphorylation of tubulin, microtubule-associated proteins, and vinculin. Under similar assay conditions, Ap4A did not inhibit phosphorylation of histone H2b by cAMP- or cGMP-dependent protein kinases. Ap4A appears to interact noncovalently with the enzyme, because removal of pp60src by immunoprecipitation from solutions containing Ap4A restored activity to uninhibited levels. A 100-fold increase in ATP (4-400 nM) caused a 13-fold increase in the 50% inhibitory concentration of Ap4A (2.5-33 microM), consistent with the interpretation that Ap4A competes for an ATP-binding site on the pp60src molecule. The simplest explanation of these results is that Ap4A binds to the phosphodonor site for ATP.
D000227:Adenine Nucleotides / Q000494:pharmacology*; D000818:Animals; D002460:Cell Line; D002471:Cell Transformation, Neoplastic; D000242:Cyclic AMP / Q000494:pharmacology; D006152:Cyclic GMP / Q000494:pharmacology; D015226:Dinucleoside Phosphates; D007074:Immunoglobulin G / Q000378:metabolism*; D007700:Kinetics; D009374:Neoplasms, Experimental / Q000276:immunology; D015688:Oncogene Protein pp60(v-src); D010766:Phosphorylation; D011494:Protein Kinases / Q000378:metabolism*; D011817:Rabbits; D051381:Rats; D014764:Viral Proteins / Q000302:isolation & purification / Q000378:metabolism*
D000227:Adenine Nucleotides; D015226:Dinucleoside Phosphates; D007074:Immunoglobulin G; D014764:Viral Proteins; C020733:diadenosine tetraphosphate; D000242:Cyclic AMP; D011494:Protein Kinases; D015688:Oncogene Protein pp60(v-src); D006152:Cyclic GMP