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rdf:type |
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lifeskim:mentions |
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pubmed:issue |
4
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pubmed:dateCreated |
1999-3-11
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pubmed:abstractText |
The Bcr-Abl oncogene, found in Philadelphia chromosome-positive myelogenous leukemia (CML), activates Ras and triggers the stress-activated protein kinase (SAPK or Jun NH2-terminal kinase [JNK]) pathway. Interruption of Ras or SAPK activation dramatically reduces Bcr-Abl-mediated transformation. Here, we report that Bcr-Abl through a Ras-dependent pathway signals the serine/threonine protein kinase GCKR (Germinal Center Kinase Related) leading to SAPK activation. Either an oncogenic form of Ras or Bcr-Abl enhances GCKR catalytic activity and its activation of SAPK, whereas inhibition of GCKR impairs Bcr-Abl-induced SAPK activation. Bcr-Abl mutants that are impaired for GCKR activation are also unable to activate SAPK. Consistent with GCKR being a functional target in CML, GCKR is constitutively active in CML cell lines and found in association with Bcr-Abl. Our results indicate that GCKR is a downstream target of Bcr-Abl and strongly implicate GCKR as a mediator of Bcr-Abl in its transformation of cells.
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pubmed:language |
eng
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pubmed:journal |
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pubmed:citationSubset |
AIM
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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 |
0006-4971
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pubmed:author |
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pubmed:issnType |
Print
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pubmed:day |
15
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pubmed:volume |
93
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pubmed:owner |
NLM
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pubmed:authorsComplete |
Y
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pubmed:pagination |
1338-45
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pubmed:dateRevised |
2009-11-19
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pubmed:meshHeading |
pubmed-meshheading:9949177-Calcium-Calmodulin-Dependent Protein Kinases,
pubmed-meshheading:9949177-Fusion Proteins, bcr-abl,
pubmed-meshheading:9949177-Gene Expression Regulation, Neoplastic,
pubmed-meshheading:9949177-Humans,
pubmed-meshheading:9949177-JNK Mitogen-Activated Protein Kinases,
pubmed-meshheading:9949177-Leukemia, Myelogenous, Chronic, BCR-ABL Positive,
pubmed-meshheading:9949177-Mitogen-Activated Protein Kinases,
pubmed-meshheading:9949177-Mutation,
pubmed-meshheading:9949177-Protein-Serine-Threonine Kinases,
pubmed-meshheading:9949177-Signal Transduction,
pubmed-meshheading:9949177-Tumor Cells, Cultured,
pubmed-meshheading:9949177-ras Proteins
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pubmed:year |
1999
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pubmed:articleTitle |
GCKR links the Bcr-Abl oncogene and Ras to the stress-activated protein kinase pathway.
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pubmed:affiliation |
B-Cell Molecular Immunology Section, Laboratory of Immunoregulation, National Institutes of Allergy and Infectious Diseases, NIH, Bethesda, MD 20892-1876, USA.
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pubmed:publicationType |
Journal Article
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