Enzyme's second messenger contributes to cell overgrowth

September 26, 2007

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

Explore further: When liver immune cells turn bad

Related Stories

When liver immune cells turn bad

April 21, 2017

A high-fat diet and obesity turn "hero" virus-fighting liver immune cells "rogue", leading to insulin resistance, a condition that often results in type 2 diabetes, according to research published today in Science Immunology.

Macrophages shown to be essential to a healthy heart rhythm

April 20, 2017

A Massachusetts General Hospital (MGH)-led research team has identified a surprising new role for macrophages, the white blood cells primarily known for removing pathogens, cellular debris and other unwanted materials. In ...

Study in mice identifies neurons that sense touch and motion

April 20, 2017

Working with genetically engineered mice—and especially their whiskers—Johns Hopkins researchers report they have identified a group of nerve cells in the skin responsible for what they call "active touch," a combination ...

Recommended for you

Discovery offers new hope to repair spinal cord injuries

April 24, 2017

Scientists at the Gladstone Institutes created a special type of neuron from human stem cells that could potentially repair spinal cord injuries. These cells, called V2a interneurons, transmit signals in the spinal cord to ...

Motion sickness drug worsens motion perception

April 24, 2017

A new study led by Massachusetts Eye and Ear researchers found that oral promethazine, a drug commonly taken to alleviate motion sickness, temporarily worsened vestibular perception thresholds by 31 percent, lowering one's ...

0 comments

Please sign in to add a comment. Registration is free, and takes less than a minute. Read more

Click here to reset your password.
Sign in to get notified via email when new comments are made.