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rdf:type |
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lifeskim:mentions |
umls-concept:C0014822,
umls-concept:C0021757,
umls-concept:C0086597,
umls-concept:C0109317,
umls-concept:C0606868,
umls-concept:C0752312,
umls-concept:C1150579,
umls-concept:C1333340,
umls-concept:C1366882,
umls-concept:C1370600,
umls-concept:C1704259,
umls-concept:C1705767,
umls-concept:C1705791,
umls-concept:C1705987,
umls-concept:C1879547,
umls-concept:C1948023,
umls-concept:C2323499
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pubmed:issue |
42
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pubmed:dateCreated |
1999-11-19
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pubmed:abstractText |
CrkL is an SH2 and SH3 domain-containing adaptor protein implicated in pathogenesis of chronic myelogenous leukemia. Here, we demonstrate that overexpression of CrkL enhances the erythropoietin (Epo)- or interleukin (IL)-3-induced activation of Elk-1 and the c-fos gene promoter activity in 32D/EpoR-Wt cells. Moreover, the Epo-induced activation of ERK1 and ERK2 was augmented and prolonged in cells inducibly overexpressing CrkL. A moderate increase in Epo-induced activation of JNK was also observed in cells overexpressing CrkL. Overexpression of C3G enhanced the Elk-1 activation synergistically with CrkL, while a C3G mutant lacking the guanine nucleotide exchange domain showed an inhibitory effect. Studies using a dominant negative Ha-Ras mutant demonstrated that the Elk-1 and ERK2 activation enhanced by CrkL and C3G was dependent on Ras. Consistent with this, the Epo-induced activation of Ras was augmented in cells inducibly overexpressing CrkL. Most importantly, a CrkL mutant defective in the SH2 or N-terminal SH3 domain showed an inhibitory effect on the Epo-induced activation of ERK2. These data indicate that the CrkL-C3G complex plays a role in Epo- or IL-3-induced, Ras-dependent activation of the Raf/ERK pathway leading to the activation of Elk-1 and the c-fos gene transcription.
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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 |
http://linkedlifedata.com/resource/pubmed/chemical/Adaptor Proteins, Signal Transducing,
http://linkedlifedata.com/resource/pubmed/chemical/CRKL protein,
http://linkedlifedata.com/resource/pubmed/chemical/DNA-Binding Proteins,
http://linkedlifedata.com/resource/pubmed/chemical/Elk1 protein, mouse,
http://linkedlifedata.com/resource/pubmed/chemical/Erythropoietin,
http://linkedlifedata.com/resource/pubmed/chemical/Guanine Nucleotide-Releasing...,
http://linkedlifedata.com/resource/pubmed/chemical/Interleukin-3,
http://linkedlifedata.com/resource/pubmed/chemical/Nuclear Proteins,
http://linkedlifedata.com/resource/pubmed/chemical/Proto-Oncogene Proteins,
http://linkedlifedata.com/resource/pubmed/chemical/Recombinant Proteins,
http://linkedlifedata.com/resource/pubmed/chemical/Transcription Factors,
http://linkedlifedata.com/resource/pubmed/chemical/ets-Domain Protein Elk-1,
http://linkedlifedata.com/resource/pubmed/chemical/ras Proteins
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pubmed:status |
MEDLINE
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pubmed:month |
Oct
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pubmed:issn |
0021-9258
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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 |
274
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pubmed:owner |
NLM
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pubmed:authorsComplete |
Y
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pubmed:pagination |
30154-62
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pubmed:dateRevised |
2011-11-17
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pubmed:meshHeading |
pubmed-meshheading:10514505-Adaptor Proteins, Signal Transducing,
pubmed-meshheading:10514505-Animals,
pubmed-meshheading:10514505-Bone Marrow Cells,
pubmed-meshheading:10514505-DNA-Binding Proteins,
pubmed-meshheading:10514505-Enzyme Activation,
pubmed-meshheading:10514505-Erythropoietin,
pubmed-meshheading:10514505-Genes, fos,
pubmed-meshheading:10514505-Guanine Nucleotide-Releasing Factor 2,
pubmed-meshheading:10514505-Interleukin-3,
pubmed-meshheading:10514505-MAP Kinase Signaling System,
pubmed-meshheading:10514505-Mice,
pubmed-meshheading:10514505-Nuclear Proteins,
pubmed-meshheading:10514505-Promoter Regions, Genetic,
pubmed-meshheading:10514505-Proto-Oncogene Proteins,
pubmed-meshheading:10514505-Recombinant Proteins,
pubmed-meshheading:10514505-Transcription Factors,
pubmed-meshheading:10514505-ets-Domain Protein Elk-1,
pubmed-meshheading:10514505-ras Proteins,
pubmed-meshheading:10514505-src Homology Domains
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pubmed:year |
1999
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pubmed:articleTitle |
CrkL mediates Ras-dependent activation of the Raf/ERK pathway through the guanine nucleotide exchange factor C3G in hematopoietic cells stimulated with erythropoietin or interleukin-3.
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pubmed:affiliation |
First Department of Internal Medicine, Tokyo Medical and Dental University, 1-5-45 Yushima, Bunkyo-ku, Tokyo 113, Japan.
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pubmed:publicationType |
Journal Article,
Research Support, Non-U.S. Gov't
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