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Embargoed by Science for 2 p.m. EST Thursday, Nov. 29, 2001
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Identify Protein With Dual Role
The unique dual-action
role of a natural regulatory protein that controls cellular function has been
described by researchers at the University of California, San Diego (UCSD)
School of Medicine in a study published in the November 30, 2001 issue of the
This is the first
scientific evidence that links an important regulatory protein to both cell
signaling (a complex cellular communication process) and membrane trafficking
(the movement of substances through the cell’s outer membrane to targeted
areas within the cell).
According to senior
author Marilyn Farquhar, Ph.D., chair of UCSD’s Department of Cellular and
Molecular Medicine, the findings are important to the scientific community
because they link previously unconnected areas and offer new avenues of
“For example,” she
added, “these findings offer potential targets for the development of new
drugs to help people with heart failure, hormone imbalances and cancer, which
are all linked to flaws in cell signaling or trafficking.”
In its cell-signaling
role, RGS-PX1 regulates a molecular on-off switch called a G protein alpha (Ga)
subunit, which is important for cellular processes that affect a variety of
conditions such as normal heart beat, hormone secretion, and kidney function.
When RGS-PX1 is present, the Ga subunit activity is turned off.
Bin Zheng, M.S., a
graduate student in UCSD’s Molecular Pathology Graduate Program and the
study’s first author, noted that RGS-PX1 also modulates trafficking within
the cell, specifically the movement of cellular components called growth
factor receptors, which influence cell growth and division.
In normal activity,
when cell growth is completed, growth factor receptors cease their activity.
RGS-PX1 delays the natural degradation of growth factor receptors and,
instead, allows cells to continue to proliferate, such as in the growth of
“Now we need more
studies to determine other molecules involved and how RGS-PX1 is activated in
its regulation of cell signaling and growth factor trafficking,” Zheng said.
Farquhar likened it to
the electrical circuits in a house where the current comes in one main
circuit, then branches out to different rooms.
are like that,” she said. “Right now we’re in the family room, where we
discovered the protein. We’re now trying to work our way back to the
entry point where this is controlled, to better understand how and why RGS-PX1
Found in yeast, plants
and mammals, there are at least 20 RGS proteins that were first described by
researchers about six years ago. The Farquhar team found one of the
first RGS proteins and has continued their studies since then. About two years
ago, Zheng found the RGS-PX1 protein while searching many of the new protein
and DNA sequence databases, then determined its function with laboratory
studies of various animal cells. The team named the protein RGS-PX1 to
include both its roles: RGS for the G protein signaling function, and PX to
signify its physical structure related to trafficking.
Additional authors of
the study were Gordon Gill, M.D., professor and interim dean for scientific
affairs, UCSD School of Medicine; Paul A. Insel, M.D., professor, and Rennolds
S. Ostrom, Ph.D., post doctoral fellow, UCSD Department of Pharmacology;
Christine Lavoie, Ph.D., assistant project pharmacologist, UCSD Department of
Cellular and Molecular Medicine; and Yong-Chao Ma, Ph.D., post doctoral fellow
and Xin-Yun Huang, Ph.D., professor, Department of Physiology, Weill Medical
College of Cornell University.
The research was
funded by the National Institutes of Health.
Copyright ©2001 Regents of the University of California. All rights reserved.