Diverse biologic properties imparted by the c-fgr proto-oncogene.
The c-fgr proto-oncogene specifies a nonreceptor protein-tyrosine kinase, p55c-fgr, a member of the src family. In the present study, we have mutagenized c-fgr to mimic alterations found at the 3' end of the v-fgr oncogene and have investigated the biologic effects of normal and mutant p55c-fgr expression. Genes lacking 10 or 13 codons at the 3' end, as well as a gene encoding phenylalanine instead of tyrosine at codon 523, were potent oncogenes when transfected into NIH 3T3 cells. Specific enzymatic activities of the more highly transforming gene products were 3-4-fold greater than that of p55c-fgr. In vivo, the amount of tyrosine phosphorylation of cellular proteins was directly proportional to potency in focus-forming assays. These findings are the first to identify highly transforming mutations of the c-fgr proto-oncogene. The proto-oncogene was also active in transforming assays, demonstrably greater than that of a kinase-deficient mutant. Foci arising in c-fgr-transfected cultures expressed abundant enzyme that was normal by a number of criteria. In addition, growth rates for cells expressing p55c-fgr were restricted, as compared with cells expressing a kinase-deficient protein or cells transformed by proteins with high specific enzymatic activities. Thus, enzymatically active p55c-fgr can simultaneously activate transforming and growth inhibitory pathways.
Sartor
O
O
Laboratory of Cellular Development and Oncology, National Institute of Dental Research, National Institutes of Health, Bethesda, Maryland 20892.
Moriuchi
R
R
Sameshima
J H
JH
Severino
M
M
Gutkind
J S
JS
Robbins
K C
KC
D016475:3T3 Cells; D000818:Animals; D001483:Base Sequence; D002455:Cell Division; D002471:Cell Transformation, Neoplastic; D015870:Gene Expression; D007700:Kinetics; D051379:Mice; D008969:Molecular Sequence Data; D016297:Mutagenesis, Site-Directed; D009838:Oligodeoxyribonucleotides; D010957:Plasmids; D011505:Protein-Tyrosine Kinases / Q000235:genetics*; D011518:Proto-Oncogene Proteins / Q000096:biosynthesis / Q000235:genetics* / Q000302:isolation & purification; D011519:Proto-Oncogenes; D014162:Transfection; D019061:src-Family Kinases
D009838:Oligodeoxyribonucleotides; D011518:Proto-Oncogene Proteins; D011505:Protein-Tyrosine Kinases; C053102:proto-oncogene proteins c-fgr; D019061:src-Family Kinases