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rdf:type |
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lifeskim:mentions |
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pubmed:issue |
2
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pubmed:dateCreated |
1996-3-5
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pubmed:abstractText |
Individuals with neurofibromatosis type 1 (NF1) are predisposed to certain cancers including juvenile chronic myelogenous leukaemia (JCML). The NF1 tumour-suppressor gene encodes a protein (neurofibromin) that accelerates GTP hydrolysis on Ras proteins. Here we show that primary leukaemic cells from children with NF1 show a selective decrease in NF1-like GTPase activating protein (GAP) activity for Ras but retain normal cellular GAP activity. Leukaemic cells also show an elevated percentage of Ras in the GTP-bound conformation. JCML cells are hypersensitive to granulocyte-macrophage colony stimulating factor (GM-CSF), and we observed a similar pattern of aberrant growth in haematopoietic cells from Nf1-/- mouse embryos. These data define a specific role for neurofibromin in negatively regulating GM-CSF signaling through Ras in haematopoietic cells and they suggest that hypersensitivity to GM-CSF may be a primary event in the development of JCML.
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pubmed:grant |
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pubmed:language |
eng
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pubmed:journal |
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pubmed:citationSubset |
IM
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pubmed:chemical |
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pubmed:status |
MEDLINE
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pubmed:month |
Feb
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pubmed:issn |
1061-4036
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pubmed:author |
pubmed-author:AdlerFF,
pubmed-author:BollagGG,
pubmed-author:ClappD WDW,
pubmed-author:FreedmanM HMH,
pubmed-author:JacksTT,
pubmed-author:LangeB JBJ,
pubmed-author:McCormickFF,
pubmed-author:ShannonKK,
pubmed-author:ShihSS,
pubmed-author:ThompsonPP,
pubmed-author:ZhangY YYY
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pubmed:issnType |
Print
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pubmed:volume |
12
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pubmed:owner |
NLM
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pubmed:authorsComplete |
Y
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pubmed:pagination |
144-8
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pubmed:dateRevised |
2007-11-15
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pubmed:meshHeading |
pubmed-meshheading:8563751-Animals,
pubmed-meshheading:8563751-Cell Division,
pubmed-meshheading:8563751-Cells, Cultured,
pubmed-meshheading:8563751-Child,
pubmed-meshheading:8563751-GTPase-Activating Proteins,
pubmed-meshheading:8563751-Genes, Neurofibromatosis 1,
pubmed-meshheading:8563751-Granulocyte-Macrophage Colony-Stimulating Factor,
pubmed-meshheading:8563751-Guanosine Triphosphate,
pubmed-meshheading:8563751-Hematopoietic Stem Cells,
pubmed-meshheading:8563751-Humans,
pubmed-meshheading:8563751-Leukemia, Myelogenous, Chronic, BCR-ABL Positive,
pubmed-meshheading:8563751-Mice,
pubmed-meshheading:8563751-Neurofibromatosis 1,
pubmed-meshheading:8563751-Neurofibromin 1,
pubmed-meshheading:8563751-Proteins,
pubmed-meshheading:8563751-Signal Transduction,
pubmed-meshheading:8563751-ras GTPase-Activating Proteins,
pubmed-meshheading:8563751-ras Proteins
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pubmed:year |
1996
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pubmed:articleTitle |
Loss of NF1 results in activation of the Ras signaling pathway and leads to aberrant growth in haematopoietic cells.
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pubmed:affiliation |
Onyx Pharmaceuticals, Richmond, California 94806, USA.
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pubmed:publicationType |
Journal Article,
Research Support, U.S. Gov't, P.H.S.,
Research Support, U.S. Gov't, Non-P.H.S.,
Research Support, Non-U.S. Gov't
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