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Rac is activated by erythropoietin or interleukin-3 and is involved in activation of the Erk signaling pathway.

Authors
  • Arai, Ayako
  • Kanda, Eiichiro
  • Miura, Osamu
Type
Published Article
Journal
Oncogene
Publisher
Springer Nature
Publication Date
Apr 18, 2002
Volume
21
Issue
17
Pages
2641–2651
Identifiers
PMID: 11965537
Source
Medline
License
Unknown

Abstract

Previous studies have shown that hematopoietic cytokines, including erythropoietin (Epo) and interleukin (IL)-3, activate the Ras GTPase and the downstream Raf/Erk/Elk-1 signaling pathway. Here we report that Epo or IL-3 rapidly and transiently activates Rac, a Rho family GTPase, in hematopoietic cell lines, 32D/EpoR-Wt and UT-7. The cytokine-induced activation of Rac was augmented in a 32D/EpoR-Wt clone that inducibly overexpresses the adaptor protein CrkL or the Ras guanine nucleotide exchange factor C3G, which forms a complex with CrkL. Furthermore, the Rac activation was enhanced or inhibited in cells inducibly expressing an activated Ras mutant, H-Ras61L, or a dominant negative Ras mutant, H-Ras17N, respectively. In addition, the cytokine-induced Rac activation was inhibited by a phosphatidyl-inositol 3'-kinase (PI3K) inhibitor, LY294002, which also inhibited the Erk activation. A dominant negative Rac mutant, Rac17N, also inhibited the cytokine-induced activation of Erk as well as Elk-1. On the other hand, activation of Akt downstream of PI3K was found to play an inhibitory role in cytokine activation of Erk/Elk-1. Together, these results indicate that Rac is activated by Epo or IL-3 at downstream of the Ras/PI3K pathway in parallel with Akt and plays a role in activation of the Erk/Elk-1 signaling pathway in hematopoietic cells.

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