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P1,P4-Di(adenosine-5')tetraphosphate inhibits phosphorylation of immunoglobulin G by Rous sarcoma virus pp60src
Journal article   Open access   Peer reviewed

P1,P4-Di(adenosine-5')tetraphosphate inhibits phosphorylation of immunoglobulin G by Rous sarcoma virus pp60src

P F Maness, M E Perry and B T Levy
The Journal of biological chemistry, Vol.258(7), pp.4055-4058
04/10/1983
DOI: 10.1016/S0021-9258(18)32580-8
PMID: 6300072
url
https://doi.org/10.1016/S0021-9258(18)32580-8View
Published (Version of record) Open Access

Abstract

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.
Phosphorylation Protein Kinases - metabolism Cell Line Cyclic GMP - pharmacology Rabbits Adenine Nucleotides - pharmacology Oncogene Protein pp60(v-src) Rats Viral Proteins - metabolism Cyclic AMP - pharmacology Animals Cell Transformation, Neoplastic Neoplasms, Experimental - immunology Viral Proteins - isolation & purification Kinetics Dinucleoside Phosphates Immunoglobulin G - metabolism

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