In:
Molecular Biology of the Cell, American Society for Cell Biology (ASCB), Vol. 16, No. 8 ( 2005-08), p. 3501-3510
Abstract:
Transforming growth factor β is the prototype of a large family of secreted factors that regulate multiple biological processes. In the immune system, TGFβ acts as an anti-inflammatory and immunosuppressive molecule, whereas the cytokine interleukin (IL)-1β is a crucial mediator of inflammatory responses and induces proinflammatory genes and acute phase proteins. Here, we present evidence for the existence of a direct inhibitory interaction between the IL-1β and TGFβ signaling cascades that is not dependent on IL-1β–induced SMAD7 expression. IL-1β and its downstream mediator TAK1 inhibit SMAD3-mediated TGFβ target gene activation, whereas SMAD3 nuclear translocation and DNA binding in response to TGFβ are not affected. IL-1β transiently induces association between TAK1 and the MAD homology 2 domain of SMAD3, resulting in SMAD3 phosphorylation. Furthermore, IL-1β alleviates the inhibitory effect of TGFβ on in vitro hematopoietic myeloid colony formation. In conclusion, our data provide evidence for the existence of a direct inhibitory effect of the IL-1β-TAK1 pathway on SMAD3-mediated TGFβ signaling, resulting in reduced TGFβ target gene activation and restored proliferation of hematopoietic progenitors.
Type of Medium:
Online Resource
ISSN:
1059-1524
,
1939-4586
DOI:
10.1091/mbc.e04-11-1033
Language:
English
Publisher:
American Society for Cell Biology (ASCB)
Publication Date:
2005
detail.hit.zdb_id:
1474922-1
SSG:
12
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