Getting signals straight at Symposium 2005

October 5, 2005

Tags: Awards + Announcements

CAMBRIDGE, Mass. (October 5, 2005) - Fiona Watt is not really out to cure baldness, not even in transgenic mice.

True, Watt, a scientist with Cancer Research UK's London Research Institute, can stimulate new hair follicles in bald mice by manipulating cell signaling molecules in the skin. But hair's simply a convenient vehicle for her to study adult stem cells.

These cells respond to cocktails of signaling molecules that tell them when to divide and which lineage of offspring to produce, such as specializing as hair follicles, sebaceous (oil) glands or the various layers of skin cells.

Watt discovered that by adjusting the level of beta-catenin (a protein involved in cell-fate decisions during development) in different skin layers in the transgenic mice, she could trick hair follicles into forming in sebaceous glands or the upper layer instead of their normal, deeper layer. To her amazement, those strangely located follicles contained known biological markers for adult stem cells, even where no previous pool of adult stem cells existed, suggesting that it might be possible to make adult stem cells from cells that have already differentiated.

She discussed her work last week at Whitehead Symposium XXIII, "Cell Signaling: Switches, Connectors, and Circuits," held Sept. 26 at MIT and drawing over 700 attendees. The meeting brought together leading biologists to discuss new findings, sometimes just days old, about cell signaling molecules, the receptors that bind them, and the proteins within cells that integrate signals into cell-specific responses.

Steven McKnight of the University of Texas Southwestern Medical Center in Dallas discussed how his group created transgenic mice lacking the NPAS1 and NPAS3 genes that were skittish, anti-social animals with numerous behaviors reminiscent of human schizophrenia. NPAS3 deficiency apparently drives a cellular pathway including the enzyme Sprouty. McNight showed that this very large protein probably acts like a nanobattery, with enough power to demethylate DNA-a critical move during embryonic development and stem cell growth.

In other presentations:

• Susan Taylor of the University of California, San Diego revealed new discoveries – and images – of the crystallized molecular structure of the best-known protein kinase, cAMP-dependent PKA, which serves as a model for studying other kinases. She showed how this kinase specifically recognizes its protein targets.

• Tony Pawson of Mt. Sinai Hospital in Toronto described how he could change the gait of mice by blocking an adaptor protein (NCK) involved in axon guidance of spinal cord neurons. Adaptor proteins “couple” many cell surface receptors to kinases and other signaling proteins mediating molecular interactions involved in, among other things, T-cell signaling, a kidney disease, cancer and walking.

• Steven Wiley explained how his research at the Pacific Northwest National Laboratory in Washington State on epidermal growth factor receptors, which can run amok in cancer, is defining the central role of an autocrine growth signaling loop, by which a hormone is produced by a cell and then binds to surface receptors on the same cell.

• George Thomas of the University of Cincinnati Genome Institute discussed his unexpected finding of a novel signaling pathway that activates a kinase, S6K1, a cell-growth signal that is very sensitive to nutrients and insulin. Mice lacking the S6 molecule can eat a huge, high fat diet without gaining an ounce.

• Robert Lefkowitz of Duke University Medical Center presented important results about still another signaling molecule, arrestin. Arrestin binds to a large class of activated G-coupled protein receptors (GPRs), inhibiting certain signaling pathways but surprisingly activating others. These receptors are the prime target for existing drugs, and his discovery of an alternate route to block or engage GPRs might lead toward new drug designs.


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