Abstract
Some tumor cell lines secrete high concentrations of TGFβ or IL-1. Similarly high concentrations of each of these cytokines cross-activate the other pathway: TGFβ activates NFκB, and IL-1β activates Smads. The IL-1 signaling components IRAK, MyD88, TRAF6, and TAK1 are all required for cross-activation of NFκB by TGFβ. Knockdown experiments revealed that both TGFβ receptor subunits are required for IL-1β to activate Smads, and the IL-1 receptor is required for TGFβ to activate NFκB. Coimmunoprecipitations showed that either TGFβ or IL-1β stimulate ligand-dependent association of all three receptor subunits. Furthermore, cross-talk between the TGFβ and IL-1 signaling pathways leads to dose-dependent cross-control of gene expression. These interactions provide new insight into biological responses to IL-1 and TGFβ in the proximity of tumors that secrete high concentrations of these factors and probably also at sites of inflammation, where the local concentrations of these cytokines are likely to be high.
| Original language | English (US) |
|---|---|
| Pages (from-to) | 4365-4370 |
| Number of pages | 6 |
| Journal | Proceedings of the National Academy of Sciences of the United States of America |
| Volume | 104 |
| Issue number | 11 |
| DOIs | |
| State | Published - Mar 13 2007 |
| Externally published | Yes |
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Keywords
- Cytokine receptors
- NFκB
- Smad
- TLRs
ASJC Scopus subject areas
- Genetics
- General
Cite this
Dose-dependent cross-talk between the transforming growth factor-β and interleukin-1 signaling pathways. / Lu, Tao; Tian, Liping; Han, Yulong; Vogelbaum, Michael; Stark, George R.
In: Proceedings of the National Academy of Sciences of the United States of America, Vol. 104, No. 11, 13.03.2007, p. 4365-4370.Research output: Contribution to journal › Article
}
TY - JOUR
T1 - Dose-dependent cross-talk between the transforming growth factor-β and interleukin-1 signaling pathways
AU - Lu, Tao
AU - Tian, Liping
AU - Han, Yulong
AU - Vogelbaum, Michael
AU - Stark, George R.
PY - 2007/3/13
Y1 - 2007/3/13
N2 - Some tumor cell lines secrete high concentrations of TGFβ or IL-1. Similarly high concentrations of each of these cytokines cross-activate the other pathway: TGFβ activates NFκB, and IL-1β activates Smads. The IL-1 signaling components IRAK, MyD88, TRAF6, and TAK1 are all required for cross-activation of NFκB by TGFβ. Knockdown experiments revealed that both TGFβ receptor subunits are required for IL-1β to activate Smads, and the IL-1 receptor is required for TGFβ to activate NFκB. Coimmunoprecipitations showed that either TGFβ or IL-1β stimulate ligand-dependent association of all three receptor subunits. Furthermore, cross-talk between the TGFβ and IL-1 signaling pathways leads to dose-dependent cross-control of gene expression. These interactions provide new insight into biological responses to IL-1 and TGFβ in the proximity of tumors that secrete high concentrations of these factors and probably also at sites of inflammation, where the local concentrations of these cytokines are likely to be high.
AB - Some tumor cell lines secrete high concentrations of TGFβ or IL-1. Similarly high concentrations of each of these cytokines cross-activate the other pathway: TGFβ activates NFκB, and IL-1β activates Smads. The IL-1 signaling components IRAK, MyD88, TRAF6, and TAK1 are all required for cross-activation of NFκB by TGFβ. Knockdown experiments revealed that both TGFβ receptor subunits are required for IL-1β to activate Smads, and the IL-1 receptor is required for TGFβ to activate NFκB. Coimmunoprecipitations showed that either TGFβ or IL-1β stimulate ligand-dependent association of all three receptor subunits. Furthermore, cross-talk between the TGFβ and IL-1 signaling pathways leads to dose-dependent cross-control of gene expression. These interactions provide new insight into biological responses to IL-1 and TGFβ in the proximity of tumors that secrete high concentrations of these factors and probably also at sites of inflammation, where the local concentrations of these cytokines are likely to be high.
KW - Cytokine receptors
KW - NFκB
KW - Smad
KW - TLRs
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UR - http://www.scopus.com/inward/citedby.url?scp=34248384441&partnerID=8YFLogxK
U2 - 10.1073/pnas.0700118104
DO - 10.1073/pnas.0700118104
M3 - Article
VL - 104
SP - 4365
EP - 4370
JO - Proceedings of the National Academy of Sciences of the United States of America
JF - Proceedings of the National Academy of Sciences of the United States of America
SN - 0027-8424
IS - 11
ER -