Signaling

Signaling Across Pathways

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Science  28 Jan 2011:
Vol. 331, Issue 6016, pp. 378
DOI: 10.1126/science.331.6016.378-b
CREDIT: JACOB ET AL., SCI. SIGNAL. 4, RA4 (2011)

The signaling pathways that regulate cell function are obvious targets for therapeutic intervention, but such strategies are complicated by our incomplete understanding of these pathways and also the links between them. Jacob et al. used an RNA interference screen in mouse cells to find new components of the Wnt and Hedgehog signaling pathways. Both are key regulatory pathways in development that are also linked to various diseases, including cancer. Loss of the protein kinase Lkb1 inhibited Hedgehog pathway–dependent gene expression through effects on the primary cilium, where Hedgehog signaling is organized. Loss of Lkb1 also disrupted Wnt signaling, but through a distinct mechanism. Similar results were observed when expression of Lkb1 was inhibited in zebrafish embryos. Similar expanded approaches thus appear necessary to understand the functions of key signaling components and how they might be managed to affect complex diseases.

Sci. Signal. 4, ra4 (2011).

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