Enzyme's second messenger contributes to cell overgrowth

Scientists at the University of California, San Diego (UCSD) School of Medicine have uncovered a novel pathway by which hormones elevated in inflammation, cancer and cell injury act on cells to stimulate their growth.

The research team led by Joan Heller Brown, Ph.D., professor and chair of the department of pharmacology at UCSD, has demonstrated in a mouse model that a newly discovered subtype of the phospholipase C (PLC) family of enzymes, called PLC-epsilon, has the unique ability to activate a second and distinct signaling pathway that cells require for proliferation. The study is currently on line in advance of publication by the Proceedings of the National Academy of Science.

The studies reported in the PNAS demonstrate that “in the cell, hormones that activate small G proteins are highly dependent on PLC-º to generate second messengers,” said Heller Brown. “In addition, and more surprisingly, we discovered that this enzyme is required for cell growth because it serves a second function when activated by hormones.”

Many intracellular signaling proteins work as molecular “switches.” The reception of a signal activates them and causes them to pass the signal through the cell, after which they can be switched off until another signal is received. G proteins are a commonly used form of switch, activated by the binding of guanine nucleotides.

PLC’s normal role is delivering signals from outside the cell to inside the cell by generating “second messengers” that tell cells to contract and secrete. But these signals alone are not enough to cause cells to increase their growth. The first author of the paper, Simona Citro, Ph.D., and colleagues found that PLC-º uniquely activates a second and distinctly different signaling cascade. This second signal catalyzes activation of a Ras family of small G proteins associated with cell growth.

“In combination with the first set of signals, this can lead to cell proliferation and could contribute to inflammation or cancer if left unchecked,” said Citro.

“PLC plays a critical role in physiological processes including heart function, cell secretion and blood pressure control, so one would not normally want to block its activity,” added Heller Brown. The UCSD researchers’ discovery may enable scientists to target this novel PLC isoform or inhibit only its second function, preventing pathological responses while leaving PLC’s critical positive role intact.

Source: University of California - San Diego

Related stories:

Warming up for Magnetic Resonance Imaging
Standard magnetic resonance imaging, MRI, is a superb diagnostic tool but one that suffers from low sensitivity, requiring patients to remain motionless for long periods of time inside noisy, claustrophobic machines. A promising new MRI method, much faster, more selective — able to distinguish even among specific target molecules — and many thousands of times more sensitive, has now been developed in the laboratory by researchers at the Department of Energy's Lawrence Berkeley National Laboratory and the University of California at Berkeley.
Surprising discovery: Multicellular response is 'all for one'
Real or perceived threats can trigger the well-known “fight or flight response” in humans and other animals. Adrenaline flows, and the stressed individual’s heart pumps faster, the muscles work harder, the brain sharpens and non-essential systems shut down. The whole organism responds in concert in order to survive.
St. Jude finds 'dancing' hair cells are key to humans' acute hearing
St. Jude Children's Research Hospital investigators have found that an electrically powered amplification mechanism in the cochlea of the ear is critical to the acute hearing of humans and other mammals. The findings will enable better understanding of how hearing loss can result from malfunction of this amplification machinery due to genetic mutation or overdose of drugs such as aspirin.
Undergrad has sweet success with invention of artificial Golgi
An undergraduate student at Rensselaer Polytechnic Institute has learned very quickly that a spoonful of sugar really does help the medicine go down. In fact, with his invention, the sugar may actually be the medicine.
Killer competition: Neurons duke it out for survival
The developing nervous system makes far more nerve cells than are needed to ensure target organs and tissues are properly connected to the nervous system. As nerves connect to target organs, they somehow compete with each other resulting in some living and some dying. Now, using a combination of computer modeling and molecular biology, neuroscientists at Johns Hopkins have discovered how the target tissue helps newly connected peripheral nerve cells strengthen their connections and kill neighboring nerves. The study was published in the April 18th issue of Science.
Test of maturity for stem cells
Stem cells are extremely versatile: They can develop in 220 different ways, transforming themselves into a correspondingly diverse range of specialized body cells. Biologists and medical scientists plan to make use of this differentiation ability to selectively harvest cardiac, skin or nerve cells for the treatment of different diseases.
Nanotube production leaps from sooty mess in test tube to ready formed chemical microsensors
Carbon nanotubes’ potential as a super material is blighted by the fact that when first made they often take the form of an unprepossessing pile of sooty black mess in the bottom of a test tube. Now researchers in the University of Warwick’s Department of Chemistry have found a way of producing carbon nanotubes in which they instantly form a highly sensitive ready made electric circuit.
Researcher reveals new model for embryonic limb development
A study led by a researcher at the University of Southern California has found a new model to explain how signals between cells in the embryo control limb development.

News discussion:

Medicine & Health news