| | |  | | | | Record from Web of Science® | | | | | | |
| The response of human epithelial cells to TNF involves an inducible autocrine cascade |
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| Author(s): Janes KA, Gaudet S, Albeck JG, Nielsen UB, Lauffenburger DA, Sorger PK |
| Source: CELL Volume: 124 Issue: 6 Pages: 1225-1239 Published: MAR 24 2006 |
| Times Cited: 60 References: 58 |
| Abstract: Tumor necrosis factor (TNF) is a proinflammatory cytokine that induces conflicting pro- and antiapoptotic signals whose relative strengths determine the extent of cell death. TNF receptor (TNFR) has been studied in considerable detail, but it is not known how crosstalk among antagonistic pro- and antiapoptotic signals is achieved. Here we report an experimental and computational analysis of crosstalk between prodeath TNF and prosurvival growth factors in human epithelial cells. By applying classifier-based regression to a cytokine-signaling compendium of similar to 8000 intracellular protein measurements, we demonstrate that cells respond to TNF both directly, via activated TNF receptor, and indirectly, via the sequential release of transforming growth factor-alpha (TGF-alpha), interleukin-1 alpha (IL-1 alpha), and IL-1 receptor antagonist (IL-1ra.). We refer to the contingent and time-varying series of extracellular signals induced by TNF as an "autocrine cascade." Time-dependent crosstalk of synergistic and antagonistic autocrine circuits may serve to link cellular responses to the local environment. |
| Document Type: Article |
| Language: English |
| Reprint Address: Sorger, PK (reprint author), MIT, Ctr Cell Decis Proc, 77 Massachusetts Ave, Cambridge, MA 02139 USA |
Addresses:
1. MIT, Ctr Cell Decis Proc, Cambridge, MA 02139 USA
2. MIT, Dept Biol Engn, Cambridge, MA 02139 USA
3. MIT, Dept Biol, Cambridge, MA 02139 USA
4. Merrimack Pharamceut, Cambridge, MA 02139 USA |
| Publisher: CELL PRESS, 1100 MASSACHUSETTS AVE, CAMBRIDGE, MA 02138 USA |
| Subject Category: Biochemistry & Molecular Biology; Cell Biology |
| IDS Number: 038RS |
| ISSN: 0092-8674 |
| DOI: 10.1016/j.cell.2006.01.041 |
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