| RRC ID |
12186
|
| 著者 |
Nosaka Y, Arai A, Miyasaka N, Miura O.
|
| タイトル |
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.
|
| ジャーナル |
J Biol Chem
|
| Abstract |
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.
|
| 巻・号 |
274(42)
|
| ページ |
30154-62
|
| 公開日 |
1999-10-15
|
| DOI |
10.1074/jbc.274.42.30154
|
| PII |
S0021-9258(19)51878-6
|
| PMID |
10514505
|
| MeSH |
Adaptor Proteins, Signal Transducing*
Animals
Bone Marrow Cells / drug effects*
Bone Marrow Cells / enzymology
Bone Marrow Cells / metabolism
DNA-Binding Proteins*
Enzyme Activation
Erythropoietin / pharmacology*
Genes, fos
Guanine Nucleotide-Releasing Factor 2 / metabolism*
Interleukin-3 / pharmacology*
MAP Kinase Signaling System*
Mice
Nuclear Proteins / metabolism*
Promoter Regions, Genetic
Proto-Oncogene Proteins / metabolism
Recombinant Proteins / pharmacology
Transcription Factors*
ets-Domain Protein Elk-1
ras Proteins / metabolism*
src Homology Domains
|
| IF |
4.238
|
| 引用数 |
50
|
|
WOS 分野
|
BIOCHEMISTRY & MOLECULAR BIOLOGY
|
| リソース情報 |
| 遺伝子材料 |
pZRmERK2 (RDB01796) |
