Document Detail


Transforming potential of the c-fms proto-oncogene (CSF-1 receptor).
MedLine Citation:
PMID:  3027579     Owner:  NLM     Status:  MEDLINE    
Abstract/OtherAbstract:
The c-fms proto-oncogene encodes a transmembrane glycoprotein that is probably identical to the receptor for the macrophage colony stimulating factor, CSF-1. Forty C-terminal amino acids of the normal receptor are replaced by 11 unrelated residues in the feline v-fms oncogene product, deleting a C-terminal tyrosine residue (Tyr969) whose phosphorylation might negatively regulate the receptor kinase activity. We show that the human c-fms gene stimulates growth of mouse NIH 3T3 cells in agar in response to human recombinant CSF-1, indicating that receptor transduction is sufficient to induce a CSF-1 responsive phenotype. Although cells transfected with c-fms genes containing either Tyr969 or Phe969 were not transformed, cotransfection of these genes with CSF-1 complementary DNA induced transformation, with c-fms(Phe969) showing significantly more activity than c-fms(Tyr969). In the absence of CSF-1, chimaeric v-fms/c-fms genes encoding the wild-type c-fms C terminus were poorly transforming, whereas chimaeras bearing Phe969 were as transforming as v-fms. Thus, the Phe969 mutation, although not in itself sufficient to induce transformation, activates the oncogenic potential of c-fms in association with an endogenous ligand or in conjunction with mutations elsewhere in the c-fms gene that confer ligand-independent signals for growth.
Authors:
M F Roussel; T J Dull; C W Rettenmier; P Ralph; A Ullrich; C J Sherr
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Publication Detail:
Type:  Comparative Study; Journal Article; Research Support, Non-U.S. Gov't; Research Support, U.S. Gov't, P.H.S.    
Journal Detail:
Title:  Nature     Volume:  325     ISSN:  0028-0836     ISO Abbreviation:  Nature     Publication Date:    1987 Feb 5-11
Date Detail:
Created Date:  1987-03-24     Completed Date:  1987-03-24     Revised Date:  2009-11-19    
Medline Journal Info:
Nlm Unique ID:  0410462     Medline TA:  Nature     Country:  ENGLAND    
Other Details:
Languages:  eng     Pagination:  549-52     Citation Subset:  IM    
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MeSH Terms
Descriptor/Qualifier:
Amino Acid Sequence
Animals
Cell Line
Cell Transformation, Neoplastic / genetics
Colony-Stimulating Factors
Fibroblasts
Glycoproteins / genetics,  physiology
Humans
Membrane Proteins / genetics,  physiology
Mice
Oncogene Protein gp140(v-fms)
Phosphorylation
Proto-Oncogene Proteins / genetics,  physiology*
Receptor, Macrophage Colony-Stimulating Factor
Receptors, Cell Surface / genetics,  physiology*
Receptors, Colony-Stimulating Factor
Recombinant Proteins / genetics,  pharmacology
Retroviridae Proteins / genetics
Sequence Homology, Nucleic Acid
Transfection
Grant Support
ID/Acronym/Agency:
CA 38187/CA/NCI NIH HHS; RR-05584/RR/NCRR NIH HHS
Chemical
Reg. No./Substance:
0/Colony-Stimulating Factors; 0/Glycoproteins; 0/Membrane Proteins; 0/Oncogene Protein gp140(v-fms); 0/Proto-Oncogene Proteins; 0/Receptors, Cell Surface; 0/Receptors, Colony-Stimulating Factor; 0/Recombinant Proteins; 0/Retroviridae Proteins; EC 2.7.10.1/Receptor, Macrophage Colony-Stimulating Factor

From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine


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