Reassessment of the v-fms sequence: threonine phosphorylation of the COOH-terminal domain.
The v-fms oncogene product of the McDonough strain of feline sarcoma virus is a member of the receptor tyrosine kinase family. Its cellular counterpart, the c-fms product, is the receptor for colony-stimulating factor 1 (CSF-1) of macrophages. We have reanalyzed the v-fms gene by direct sequencing of a biologically active clone. An additional A nucleotide was detected in position 2810 of the published v-fms sequence. The frameshift changed the COOH-terminal sequence of the v-fms protein from -R-937-G-P-P-L-COOH to -Q-937-R-T-P-P-V-A-R-COOH. Antibodies against a synthetic peptide representing this new sequence precipitated the v-fms proteins from transformed NRK cells as well as from feline sarcoma virus (McDonough)-infected feline fibroblasts. We show by tryptic peptide mapping that threonine 939 present in the new sequence is phosphorylated by a yet unknown serine/threonine kinase in vivo. In chicken fibroblasts expressing the v-fms gene, this phosphorylation clearly depended on the addition of exogenous CSF-1. Furthermore, addition of CSF-1 appeared to activate the serine/threonine kinase, as judged by phosphorylation of the synthetic peptide QRTPPVAR.
Smola
U
U
Institut für Virologie, Justus-Liebig-Universität Giessen, Germany.
Hennig
D
D
Hadwiger-Fangmeier
A
A
Schütz
B
B
Pfaff
E
E
Niemann
H
H
Tamura
T
T
D000595:Amino Acid Sequence; D000818:Animals; D001483:Base Sequence; D002415:Cats; D002460:Cell Line; D002461:Cell Line, Transformed; D008969:Molecular Sequence Data; D016281:Oncogene Protein gp140(v-fms) / Q000235:genetics* / Q000378:metabolism; D009857:Oncogenes; D010766:Phosphorylation; D011505:Protein-Tyrosine Kinases / Q000235:genetics* / Q000378:metabolism; D016186:Receptor, Macrophage Colony-Stimulating Factor / Q000378:metabolism; D012190:Retroviridae / Q000235:genetics*; D013379:Substrate Specificity
D016281:Oncogene Protein gp140(v-fms); D011505:Protein-Tyrosine Kinases; D016186:Receptor, Macrophage Colony-Stimulating Factor