Getting signals straight at Symposium
2005
How do organisms carry out signaling between and
within their cells? Leading biologists detail new advances
in understanding cell circuitry.
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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