Purification and characterization of a protein-tyrosine kinase encoded by the Abelson murine leukemia virus

J Biol Chem. 1985 Jul 5;260(13):8070-7.

Abstract

Sequences termed v-abl, which encode the protein-tyrosine kinase activity of Abelson murine leukemia virus, have been expressed in Escherichia coli as a fusion product (ptabl50 kinase). This fusion protein contains 80 amino acids of SV40 small t and the 403 amino acid protein kinase domain of v-abl. We report here the purification and characterization of this kinase. The purified material contains two proteins (Mr = 59,800 and 57,200), both of which possess sequences derived from v-abl. Overall purification was 3,750-fold, with a 31% yield, such that 117 micrograms of kinase could be obtained from 40 g of E. coli within 6-7 days. The specific kinase activity is over 170 mumol of phosphate min-1 mumol-1, comparable to the most active protein-serine kinases. Kinase activity is insensitive to K+, Na+, Ca2+, Ca2+-calmodulin, cAMP, or cAMP-dependent protein kinase inhibitor. The Km for ATP is dependent on the concentration of the second substrate. GTP can also be used as a phosphate donor. The enzyme can phosphorylate peptides consisting of as few as two amino acids and, at a very low rate, free tyrosine. Incubation of the kinase with [gamma-32P]ATP results in incorporation of 1.0 mol of phosphate/mol of protein. This reaction, however, cannot be blocked by prior incubation with unlabeled ATP. Incubation of 32P-labeled kinase with either ADP or ATP results in the synthesis of [32P]ATP. This suggests the phosphotyrosine residue on the Abelson kinase contains a high energy phosphate bond.

Publication types

  • Research Support, Non-U.S. Gov't
  • Research Support, U.S. Gov't, P.H.S.

MeSH terms

  • Abelson murine leukemia virus / enzymology*
  • Abelson murine leukemia virus / genetics
  • Adenosine Triphosphate / metabolism
  • Angiotensin II / metabolism
  • Cell Transformation, Viral*
  • DNA, Viral / analysis
  • Edetic Acid / pharmacology
  • Escherichia coli
  • Kinetics
  • Leukemia Virus, Murine / enzymology*
  • Magnesium / pharmacology
  • Manganese / pharmacology
  • Molecular Weight
  • Osmolar Concentration
  • Phosphorylation
  • Protein Kinases / genetics
  • Protein Kinases / isolation & purification*
  • Protein-Tyrosine Kinases
  • Tyrosine / metabolism

Substances

  • DNA, Viral
  • Angiotensin II
  • Tyrosine
  • Manganese
  • Adenosine Triphosphate
  • Edetic Acid
  • Protein Kinases
  • Protein-Tyrosine Kinases
  • Magnesium