Leucine zipper-like domain regulates the autophosphorylation and the transforming activity of P130gag-fps.
P130gag-fps, the product of Fujinami sarcoma virus, has a leucine zipper (LZ) motif located in 729-756 amino acid residues. To explore the role of LZ-like domain in the transformation by P130gag-fps, we made a deletion (delta FpsLZ/SH2) and a site-directed substitution mutation (L746P). Deletion mutant did not transform the 3Y1 cells and the resulting protein did not show kinase activity. Substitution of Leu746 with Pro (L746P) reduced the transforming activity by 6-fold. Although the L746P mutant retained intact catalytic activity in vitro, it did not phosphorylate cellular proteins in vivo. We concluded that LZ-like domain might mediate the trans-activation of P130gag-fps tyrosine kinase by autophosphorylation, which is prerequisite for the transforming activity.
Park
W Y
WY
Transgenic Mice Center, Cancer Research Institute, Seoul, Korea.
Seo
J S
JS
D000595:Amino Acid Sequence; D000818:Animals; D002460:Cell Line; D002471:Cell Transformation, Neoplastic; D004622:Embryo, Mammalian; D015681:Fusion Proteins, gag-onc / Q000096:biosynthesis* / Q000378:metabolism; D015683:Gene Products, gag / Q000096:biosynthesis* / Q000378:metabolism; D015151:Immunoblotting; D007930:Leucine; D016350:Leucine Zippers; D008969:Molecular Sequence Data; D016297:Mutagenesis, Site-Directed; D010766:Phosphorylation; D017354:Point Mutation; D011392:Proline; D011505:Protein-Tyrosine Kinases / Q000096:biosynthesis; D051381:Rats; D011993:Recombinant Fusion Proteins / Q000096:biosynthesis* / Q000378:metabolism; D012190:Retroviridae; D017384:Sequence Deletion
D015681:Fusion Proteins, gag-onc; D015683:Gene Products, gag; D011993:Recombinant Fusion Proteins; D011392:Proline; D011505:Protein-Tyrosine Kinases; C068415:v-fps oncogene protein, Fujinami sarcoma virus; D007930:Leucine