Spred-1 negatively regulates interleukin-3-mediated ERK/mitogen-activated protein (MAP) kinase activation in hematopoietic cells

Atsushi Nonami, Reiko Kato, Koji Taniguchi, Daigo Yoshiga, Takaharu Taketomi, Satoru Fukuyama, Mine Harada, Atsuo Sasaki, Akihiko Yoshimura

Research output: Contribution to journalArticle

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Abstract

Sprouty/Spred family proteins have been identified as negative regulators of growth factor-induced ERK/mitogen-activated protein (MAP) kinase activation. However, it has not been clarified whether these proteins regulate cytokine-induced ERK activity. We found that Spred-1 is highly expressed in interleukin-3 (IL-3)-dependent hematopoietic cell lines and bone marrow-derived mast cells. To investigate the roles of Spred-1 in hematopoiesis, we expressed wild-type Spred-1 and a dominant negative form, of Spred-1, ΔC-Spred, in IL-3-and stem cell factor (SCF)-dependent cell lines as well as hematopoietic progenitor cells from mouse bone marrow by retrovirus gene transfer. In IL-3-dependent Ba/F3 cells expressing c-kit, forced expression of Spred-1 resulted in a reduced proliferation rate and ERK activation in response to not only SCF but also IL-3. In contrast, ΔC-Spred augmented IL-3-induced cell proliferation and ERK activation. Wild-type Spred-1 inhibited colony formation of bone marrow cells in the presence of cytokines, whereas AC-Spred-1 expression enhanced colony formation. Augmentation of ERK activation and proliferation in response to IL-3 was also observed in Spred-1-deficient bone marrow-derived mast cells. These data suggest that Spred-1 negatively regulates hematopoiesis by suppressing not only SCF-induced but also IL-3-induced ERK activation.

Original languageEnglish
Pages (from-to)52543-52551
Number of pages9
JournalJournal of Biological Chemistry
Volume279
Issue number50
DOIs
Publication statusPublished - 2004 Dec 10
Externally publishedYes

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Interleukin-3
Mitogen-Activated Protein Kinases
Chemical activation
Stem Cell Factor
Bone
Cells
Bone Marrow
Hematopoiesis
Mast Cells
Cytokines
Gene transfer
Cell Line
Cell proliferation
Retroviridae
Hematopoietic Stem Cells
Bone Marrow Cells
Intercellular Signaling Peptides and Proteins
Proteins
Cell Proliferation
Genes

ASJC Scopus subject areas

  • Biochemistry

Cite this

Spred-1 negatively regulates interleukin-3-mediated ERK/mitogen-activated protein (MAP) kinase activation in hematopoietic cells. / Nonami, Atsushi; Kato, Reiko; Taniguchi, Koji; Yoshiga, Daigo; Taketomi, Takaharu; Fukuyama, Satoru; Harada, Mine; Sasaki, Atsuo; Yoshimura, Akihiko.

In: Journal of Biological Chemistry, Vol. 279, No. 50, 10.12.2004, p. 52543-52551.

Research output: Contribution to journalArticle

Nonami, Atsushi ; Kato, Reiko ; Taniguchi, Koji ; Yoshiga, Daigo ; Taketomi, Takaharu ; Fukuyama, Satoru ; Harada, Mine ; Sasaki, Atsuo ; Yoshimura, Akihiko. / Spred-1 negatively regulates interleukin-3-mediated ERK/mitogen-activated protein (MAP) kinase activation in hematopoietic cells. In: Journal of Biological Chemistry. 2004 ; Vol. 279, No. 50. pp. 52543-52551.
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