LEUCINE ZIPPER-LIKE DOMAIN REGULATES THE AUTOPHOSPHORYLATION AND THE TRANSFORMING ACTIVITY OF P130(GAG-FPS)

P-130gag-fps, the product of Fujinami sarcoma virus, has a leucine zip per (LZ) motif located in 729-756 amino acid residues. To explore the role of LZ-like domain in the transformation by P-130gag-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 resu lting protein did not show kinase activity. Substitution of Leu746 wit h Pro (L746P) reduced the transforming activity by 6-fold. Although th e L746P mutant retained intact catalytic activity in vitro, it did not phosphorylate cellular proteins in vivo. We concluded that LZ-like do main might mediate the trans-activation of P-130gag-fps tyrosine kinas e by autophosphorylation, which is prerequisite for the transforming a ctivity. (C) 1995 Academic Press, Inc.