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: Study may explain why people with type O blood more likely to die of cholera

Related Stories

Special nerve cells cause goose bumps and nipple erection

August 29, 2016

The sympathetic nerve system has long been thought to respond the same regardless of the physical or emotional stimulus triggering it. However, in a new study from Karolinska Institutet published in the Nature Neuroscience, ...

Melanoma—mechanisms of BRAF-inhibitor resistance deciphered

August 29, 2016

BRAF mutation occurs in between 40% and 50% of metastasising melanomas (skin cancers), boosting tumour growth. Patients with metastasising melanomas and who display BRAF mutation can be treated with an inhibitor that acts ...

Harmful algal blooms in their true colors

August 29, 2016

Explosive growth of cyanobacteria, also called blue-green algae, is nothing new. In fact, such cyanobacteria probably produced the original oxygen in Earth's atmosphere billions of years ago.

Recommended for you

How the finch changes its tune

August 3, 2015

Like top musicians, songbirds train from a young age to weed out errors and trim variability from their songs, ultimately becoming consistent and reliable performers. But as with human musicians, even the best are not machines. ...

Cow embryos reveal new type of chromosome chimera

May 27, 2016

I've often wondered what happens between the time an egg is fertilized and the time the ball of cells that it becomes nestles into the uterine lining. It's a period that we know very little about, a black box of developmental ...

Shaving time to test antidotes for nerve agents

February 29, 2016

Imagine you wanted to know how much energy it took to bike up a mountain, but couldn't finish the ride to the peak yourself. So, to get the total energy required, you and a team of friends strap energy meters to your bikes ...

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.