Mutagenesis of Fujinami sarcoma virus: evidence that tyrosine phosphorylation of P130gag-fps modulates its biological activity.
The 130 kd transforming protein of Fujinami sarcoma virus (FSV P130gag -fps) possesses a tyrosine-specific protein kinase activity and is itself phosphorylated at several tyrosine and serine residues in FSV-transformed cells. We have used oligonucleotide-directed mutagenesis of the FSV genome to change the TAT codon for tyrosine (1073), the major site of P130gag -fps phosphorylation, to a TTT codon for phenylalanine that cannot be phosphorylated. This mutant FSV induces the transformation of rat-2 cells but with a long latent period as compared with wild-type FSV. The P130gag -fps protein encoded by the mutant retains the ability to phosphorylate tyrosine, but is five times less active as a kinase in vitro than wild-type FSV P130gag -fps. These data indicate that tyrosine phosphorylation stimulates the biochemical and biological activities of FSV P130gag -fps, and they set a precedent for the ability of this amino acid modification to modulate protein function.
D000595:Amino Acid Sequence; D000818:Animals; D000956:Antigens, Viral / Q000235:genetics*; D001358:Avian Sarcoma Viruses / Q000235:genetics*; D001483:Base Sequence; D002460:Cell Line; D002471:Cell Transformation, Neoplastic; D004262:DNA Restriction Enzymes; D015683:Gene Products, gag; D009154:Mutation; D010766:Phosphorylation; D011494:Protein Kinases / Q000235:genetics*; D011505:Protein-Tyrosine Kinases; D014162:Transfection; D014443:Tyrosine; D014764:Viral Proteins / Q000235:genetics*
D000956:Antigens, Viral; D015683:Gene Products, gag; D014764:Viral Proteins; D014443:Tyrosine; D011494:Protein Kinases; D011505:Protein-Tyrosine Kinases; D004262:DNA Restriction Enzymes