UCSD researchers identify protein with dual role in regulation of cellular processes

November 29, 2001

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 journal Science.

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 disease research.

"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 cancerous tumors.

"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.

"Signaling circuits 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 gets activated."

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.Caption to image #1

Sequentially, the cell signaling process begins with a G protein coupled receptor on the cell's surface. The receptor binds to an external stimulus and transmits the desired effect into the cell's interior, stimulating a G protein. Composed of three subunits - alpha, beta and gamma - the G protein divides into a G alpha subunit and G beta/gamma units, which then activate an effector (E)molecule at the end of the pathway.RGS-PX1 protein is introduced in the process, between the separated G alpha and G beta/gamma subunits, the normal process is reversed.

Caption to image #2

When molecules such as Epidermal Growth Factor (EGF) are taken up by cell, they are routed through a well-defined pathway.For example, EGF and EGF receptor aretransported through the cell in a network of tubules and vesicles called endosomes,then delivered to a lysosome, which is the terminal compartment - or designated target - of the trafficking pathway. Normally, when it reaches the lysosome, EGF and its receptor are degraded - a process critical for EGF's multiple activities including cell proliferation, differentiation and migration. RGS-PX1 stops this process and slows degradation of EGF and its receptor.

University of California - San Diego

Related Protein Articles from Brightsurf:

The protein dress of a neuron
New method marks proteins and reveals the receptors in which neurons are dressed

Memory protein
When UC Santa Barbara materials scientist Omar Saleh and graduate student Ian Morgan sought to understand the mechanical behaviors of disordered proteins in the lab, they expected that after being stretched, one particular model protein would snap back instantaneously, like a rubber band.

Diets high in protein, particularly plant protein, linked to lower risk of death
Diets high in protein, particularly plant protein, are associated with a lower risk of death from any cause, finds an analysis of the latest evidence published by The BMJ today.

A new understanding of protein movement
A team of UD engineers has uncovered the role of surface diffusion in protein transport, which could aid biopharmaceutical processing.

A new biotinylation enzyme for analyzing protein-protein interactions
Proteins play roles by interacting with various other proteins. Therefore, interaction analysis is an indispensable technique for studying the function of proteins.

Substituting the next-best protein
Children born with Duchenne muscular dystrophy have a mutation in the X-chromosome gene that would normally code for dystrophin, a protein that provides structural integrity to skeletal muscles.

A direct protein-to-protein binding couples cell survival to cell proliferation
The regulators of apoptosis watch over cell replication and the decision to enter the cell cycle.

A protein that controls inflammation
A study by the research team of Prof. Geert van Loo (VIB-UGent Center for Inflammation Research) has unraveled a critical molecular mechanism behind autoimmune and inflammatory diseases such as rheumatoid arthritis, Crohn's disease, and psoriasis.

Resurrecting ancient protein partners reveals origin of protein regulation
After reconstructing the ancient forms of two cellular proteins, scientists discovered the earliest known instance of a complex form of protein regulation.

Sensing protein wellbeing
The folding state of the proteins in live cells often reflect the cell's general health.

Read More: Protein News and Protein Current Events
Brightsurf.com is a participant in the Amazon Services LLC Associates Program, an affiliate advertising program designed to provide a means for sites to earn advertising fees by advertising and linking to Amazon.com.