Linked Life Data

9669841

Source:http://linkedlifedata.com/resource/pubmed/id/9669841

Statements in which the resource exists as a subject.
PredicateObject
rdf:type
lifeskim:mentions
pubmed:issue
4
pubmed:dateCreated
1998-8-19
pubmed:abstractText
The FMS proto-oncogene encodes the cell surface receptor for colony stimulating factor-1 (CSF-1). Mutations of the FMS gene at codon 969, in the C-terminal region of the gene, have been detected in haematological malignancies. To ascertain the biological significance of a mutation at this codon, we have used a murine haematopoietic cell line, FDC-P1, containing a mutation at codon 969 that results in a phenylalanine replacing a tyrosine. FMS 969 mutant cells and v-fms transfected cells conferred interleukin 3 (IL-3) independent stimulation of FDC-P1 cells, whereas cells transfected with a wild-type FMS construct required exogenous IL-3 for growth. FDC-P1 cells containing a FMS 969 mutation and v-fms transfected cells were tumorigenic in nude mice. Binding studies with radioidonated CSF-1 revealed saturable specific binding in FMS wild-type cells with a Km of 0.9 mM; however, mutant FMS-containing cells did not display saturation kinetics, but instead exhibited a linear relationship between ligand concentration and amount bound. Constitutive expression of FOS was detected in 969 mutant cells in the absence of exogenous CSF-1, a phenotype that was only inducible in wild-type cells in response to CSF-1. FOS and JUNB expression by v-FMS transfected cells showed a similar pattern to FMS wild-type cells. This mutation has been detected in patients with haematological malignancies, and illustrates that the pathway of FMS 969 phenylalanine mutations and v-fms induced pathogenesis can be distinguished. These data indicate that there is a biological role for FMS codon 969 phenylalanine mutation which results in transformation of FDC-P1 cells.
pubmed:language
eng
pubmed:journal
pubmed:citationSubset
IM
pubmed:chemical
pubmed:status
MEDLINE
pubmed:month
Apr
pubmed:issn
0145-2126
pubmed:author
pubmed:issnType
Print
pubmed:volume
22
pubmed:owner
NLM
pubmed:authorsComplete
Y
pubmed:pagination
365-72
pubmed:dateRevised
2009-11-19
pubmed:meshHeading
pubmed:year
1998
pubmed:articleTitle
Biological consequences of a point mutation at codon 969 of the FMS gene.
pubmed:affiliation
School of Biomedical Sciences, University of Ulster at Coleraine, N. Ireland, UK. H.McGlynn@ulst.ac.uk
pubmed:publicationType
Journal Article, Research Support, Non-U.S. Gov't