Most signaling responses map between distinct pathways.

SORGER/ELSEVIER

Cells often weigh conflicting signals. They do so in part, say Kevin Janes, Peter Sorger (MIT, Cambridge, MA), and colleagues, by generating extracellular signaling circuits that allow for group consensus.

The MIT group measured 19 signaling markers over 13 time points after cells were stimulated with different combinations of proapoptotic TNF and mitogenic insulin and EGF. The data were plotted and regressed in 19-dimensional space. “You take this space and try to reduce the number of dimensions while retaining important information,” says Sorger. The resulting two-dimensional graph showed that a few markers were solely related to signaling by one pathway, but most were clustered somewhere in between.

This crosstalk resulted in alternating pro- and antiapoptotic signals. First, TNF receptor activation induces shedding of TGFα, which turns on the EGF receptor. The two active receptors (TNFR and EGFR)...

The Rockefeller University Press
2006
The Rockefeller University Press
2006
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