Spred-1 Negatively Regulates Interleukin-3-mediated ERK/Mitogen-activated Protein (MAP) Kinase Activation in Hematopoietic Cells

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 int...

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Veröffentlicht in:The Journal of biological chemistry 2004-12, Vol.279 (50), p.52543-52551
Hauptverfasser: Nonami, Atsushi, Kato, Reiko, Taniguchi, Koji, Yoshiga, Daigo, Taketomi, Takaharu, Fukuyama, Satoru, Harada, Mine, Sasaki, Atsuo, Yoshimura, Akihiko
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container_end_page 52551
container_issue 50
container_start_page 52543
container_title The Journal of biological chemistry
container_volume 279
creator Nonami, Atsushi
Kato, Reiko
Taniguchi, Koji
Yoshiga, Daigo
Taketomi, Takaharu
Fukuyama, Satoru
Harada, Mine
Sasaki, Atsuo
Yoshimura, Akihiko
description 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 ΔC-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.
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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 ΔC-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. 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Augmentation of ERK activation and proliferation in response to IL-3 was also observed in Spred-1-deficient bone marrow-derived mast cells. 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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.</abstract><cop>United States</cop><pub>American Society for Biochemistry and Molecular Biology</pub><pmid>15465815</pmid><doi>10.1074/jbc.M405189200</doi><tpages>9</tpages><oa>free_for_read</oa></addata></record>
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subjects Adaptor Proteins, Signal Transducing
Animals
Cell Line
Colony-Forming Units Assay
Enzyme Activation
Extracellular Signal-Regulated MAP Kinases - metabolism
Gene Expression
Hematopoiesis
Hematopoietic Stem Cells - metabolism
Humans
In Vitro Techniques
Interleukin-3 - metabolism
MAP Kinase Signaling System
Mice
Mice, Inbred C57BL
Mice, Knockout
Repressor Proteins - genetics
Repressor Proteins - metabolism
Stem Cell Factor - metabolism
title Spred-1 Negatively Regulates Interleukin-3-mediated ERK/Mitogen-activated Protein (MAP) Kinase Activation in Hematopoietic Cells
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