Colony-stimulating factor 1-mediated regulation of a chimeric c-fms/v-fms receptor containing the v-fms-encoded tyrosine kinase domain

Journal Article · Mon Aug 01 04:00:00 EDT 1988 · Proceedings of the National Academy of Sciences of the United States of America; (USA)

DOI:https://doi.org/10.1073/pnas.85.16.5903· OSTI ID:5518505

Roussel, M F; Downing, J R; Ashmun, R A; Rettenmier, C W; Sherr, C J ^[1]

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1. St. Jude Children's Research Hospital, Memphis, TN (USA)

A chimeric gene specifying the 308 N-terminal amino acids of the extracellular ligand binding domain of the human c-fms protooncogene joined to the remainder of the feline v-fms oncogene product encodes a functional colony-stimulating factor 1 (CSF-1) receptor. When expressed in mouse NIH 3T3 fibroblasts, the chimeric gene product was rapidly transported to the cell surface, was autophosphorylated on tyrosine only in response to human recombinant CSF-1, underwent ligand-induced but not phorbol ester-induced down-modulation, and stimulated CSF-1-dependent cell proliferation. By contrast, the C-terminally truncated glycoprotein encoded by the v-fms oncogene is partially inhibited in its transport to the plasma membrane, is constitutively phosphorylated on tyrosine, and is relatively refractory to both ligand-induced and phorbol ester-induced down-modulation. Although the v-fms oncogene can transform cells in the absence of CSF-1, its tyrosine kinase activity and turnover can be appropriately regulated by the human c-fms-encoded ligand binding domain. The results confirm that C-terminal truncation of the c-fms gene is insufficient to activate its transforming potential and suggest that an additional mutation in its distal extracellular domain is required for oncogenic activation.

• OSTI ID: 5518505
• Journal Information: Proceedings of the National Academy of Sciences of the United States of America; (USA), Journal Name: Proceedings of the National Academy of Sciences of the United States of America; (USA) Vol. 85:16; ISSN 0027-8424; ISSN PNASA
• Country of Publication: United States
• Language: English

Related Subjects

550200* -- Biochemistry
59 BASIC BIOLOGICAL SCIENCES
AMINO ACIDS
ANIMAL CELLS
ANIMALS
BIOLOGICAL EFFECTS
CARBOHYDRATES
CARBOXYLIC ACIDS
CARCINOGENS
CELL CONSTITUENTS
CELL MEMBRANES
CHEMICAL REACTIONS
CHIMERAS
CONNECTIVE TISSUE CELLS
ENZYMES
ESTERS
FIBROBLASTS
GENE REGULATION
GENES
GLUCOPROTEINS
GLYCOPROTEINS
GROWTH FACTORS
HYDROXY ACIDS
LIGANDS
MAMMALS
MEMBRANE PROTEINS
MEMBRANES
MICE
MITOGENS
MOSAICISM
ONCOGENES
ORGANIC ACIDS
ORGANIC COMPOUNDS
PHORBOL ESTERS
PHOSPHORUS-GROUP TRANSFERASES
PHOSPHORYLATION
PHOSPHOTRANSFERASES
PROTEINS
RECEPTORS
RODENTS
SACCHARIDES
SOMATIC CELLS
TRANSFERASES
TYROSINE
VERTEBRATES