1. The role of v-Fgr myristoylation and the Gag domain in membrane binding and cellular transformation.
- Author
-
Baker SJ, Cosenza SC, and Reddy EP
- Subjects
- 3T3 Cells, Animals, Binding Sites genetics, Cats, Mice, Mutation, Protein Binding, Protein-Tyrosine Kinases genetics, Protein-Tyrosine Kinases metabolism, Sarcoma Viruses, Feline genetics, Cell Transformation, Viral genetics, Gene Products, gag genetics, Gene Products, gag metabolism, Retroviridae Proteins, Oncogenic genetics, Retroviridae Proteins, Oncogenic metabolism
- Abstract
The v-fgr oncogene encodes a chimeric oncoprotein composed of feline sarcoma virus (FeSV)-derived gag and cellular-derived actin and c-Fgr sequences. v-Fgr is myristoylated and membrane bound, two criteria which must be met for src kinases to induce cellular transformation. Although inhibition of myristoylation resulted in a decreased ability of v-Fgr to sediment with membranes from an NIH-3T3 P100 fraction, deletion of the gag domain caused nearly all of the protein to remain unbound and cytosolic. Systematic deletions within gag indicate that while amino acids 3 through 9 are critical determinants of myristoylation and/or define a domain which directs membrane localization, these residues cooperate with additional gag sequences when anchoring the protein to the plasma membrane. Furthermore, nonmyristoylated and/or cytoplasmic variants of v-Fgr failed to induce anchorage-independent growth of NIH-3T3 cells, indicating that proper subcellular localization of v-Fgr is a key factor in its ability to induce transformation., (Copyright 1998 Academic Press.)
- Published
- 1998
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