The role of v-Fgr myristoylation and the Gag domain in membrane binding and cellular transformation.
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.
Baker
S J
SJ
Fels Institute for Cancer Research and Molecular Biology, Temple University School of Medicine, 3307 North Broad Street, Philadelphia, Pennsylvania, 19140, USA.
Cosenza
S C
SC
Reddy
E P
EP
D016475:3T3 Cells; D000818:Animals; D001665:Binding Sites / Q000235:genetics; D002415:Cats; D002472:Cell Transformation, Viral / Q000235:genetics; D015683:Gene Products, gag / Q000235:genetics* / Q000378:metabolism*; D051379:Mice; D009154:Mutation; D011485:Protein Binding; D011505:Protein-Tyrosine Kinases / Q000235:genetics / Q000378:metabolism; D015682:Retroviridae Proteins, Oncogenic / Q000235:genetics* / Q000378:metabolism*; D005253:Sarcoma Viruses, Feline / Q000235:genetics
D015683:Gene Products, gag; D015682:Retroviridae Proteins, Oncogenic; C052601:v-fgr protein, Feline sarcoma virus; D011505:Protein-Tyrosine Kinases