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 |
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Zusammenfassung: | 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, ÎC-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, ÎC-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 ÎC-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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ISSN: | 0021-9258 1083-351X |
DOI: | 10.1074/jbc.M405189200 |