Roles of Stat3 and ERK in G-CSF signaling

Kenjiro Kamezaki, Kazuya Shimoda, Akihiko Numata, Takashi Haro, Haruko Kakumitsu, Masumi Yoshie, Masahiro Yamamoto, Kiyoshi Takeda, Tadashi Matsuda, Shizuo Akira, Katsuhiro Ogawa, Mine Harada

Research output: Contribution to journalArticle

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Abstract

G-CSF specifically stimulates the proliferation and differentiation of cells that are committed to the neutrophil-granulocyte lineage. Although Stat3 was thought to be essential for the transduction of G-CSF-induced cell proliferation and differentiation signals, mice deficient for Stat3 in hematopoietic cells show neutrocytosis and infiltration of cells into the digestive tract. The number of progenitor cells in the neutrophil lineage is not changed, and G-CSF-induced proliferation of progenitor cells and prolonged neutrophil survival were observed in Stat3-deficient mice. In hematopoietic cells from Stat3-deficient mice, trace levels of SOCS3, a negative regulator of granulopoiesis, were observed, and SOCS3 expression was not induced by G-CSF stimulation. Stat3-null bone marrow cells displayed a significant activation of extracellular regulated kinase 1 (ERK1)/ERK2 under basal conditions, and the activation of ERK was enhanced and sustained by G-CSF stimulation. Furthermore, the augmented proliferation of Stat3-deficient bone marrow cells in response to G-CSF was dramatically decreased by addition of a MEK1 inhibitor. These results indicate that Stat3 functions as a negative regulator of G-CSF signaling by inducing SOCS3 expression and that ERK activation is the major factor responsible for inducing the proliferation of hematopoietic cells in response to G-CSF.

Original languageEnglish
Pages (from-to)252-263
Number of pages12
JournalSTEM CELLS
Volume23
Issue number2
DOIs
Publication statusPublished - Feb 1 2005

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Granulocyte Colony-Stimulating Factor
Neutrophils
Cell Proliferation
Bone Marrow Cells
Cell Differentiation
Stem Cells
Null Lymphocytes
Granulocytes
Gastrointestinal Tract
Phosphotransferases

All Science Journal Classification (ASJC) codes

  • Molecular Medicine
  • Developmental Biology
  • Cell Biology

Cite this

Kamezaki, K., Shimoda, K., Numata, A., Haro, T., Kakumitsu, H., Yoshie, M., ... Harada, M. (2005). Roles of Stat3 and ERK in G-CSF signaling. STEM CELLS, 23(2), 252-263. https://doi.org/10.1634/stemcells.2004-0173a

Roles of Stat3 and ERK in G-CSF signaling. / Kamezaki, Kenjiro; Shimoda, Kazuya; Numata, Akihiko; Haro, Takashi; Kakumitsu, Haruko; Yoshie, Masumi; Yamamoto, Masahiro; Takeda, Kiyoshi; Matsuda, Tadashi; Akira, Shizuo; Ogawa, Katsuhiro; Harada, Mine.

In: STEM CELLS, Vol. 23, No. 2, 01.02.2005, p. 252-263.

Research output: Contribution to journalArticle

Kamezaki, K, Shimoda, K, Numata, A, Haro, T, Kakumitsu, H, Yoshie, M, Yamamoto, M, Takeda, K, Matsuda, T, Akira, S, Ogawa, K & Harada, M 2005, 'Roles of Stat3 and ERK in G-CSF signaling', STEM CELLS, vol. 23, no. 2, pp. 252-263. https://doi.org/10.1634/stemcells.2004-0173a
Kamezaki K, Shimoda K, Numata A, Haro T, Kakumitsu H, Yoshie M et al. Roles of Stat3 and ERK in G-CSF signaling. STEM CELLS. 2005 Feb 1;23(2):252-263. https://doi.org/10.1634/stemcells.2004-0173a
Kamezaki, Kenjiro ; Shimoda, Kazuya ; Numata, Akihiko ; Haro, Takashi ; Kakumitsu, Haruko ; Yoshie, Masumi ; Yamamoto, Masahiro ; Takeda, Kiyoshi ; Matsuda, Tadashi ; Akira, Shizuo ; Ogawa, Katsuhiro ; Harada, Mine. / Roles of Stat3 and ERK in G-CSF signaling. In: STEM CELLS. 2005 ; Vol. 23, No. 2. pp. 252-263.
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