Enzyme's second messenger contributes to cell overgrowth

Sep 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: A real-time tracking system developed to monitor dangerous bacteria inside the body

add to favorites email to friend print save as pdf

Related Stories

Stem cell physical

Oct 13, 2014

Looking at stem cells through physicists' eyes is challenging some of our basic assumptions about the body's master cells.

Recommended for you

Cause of ageing remains elusive

16 hours ago

A report by Chinese researchers in the journal Nature a few months ago was a small sensation: they appeared to have found the cause for why organisms age. An international team of scientists, headed by the ...

Newly discovered bacterial defence mechanism in the lungs

18 hours ago

A new study from Karolinska Institutet presents a previously unknown immunological mechanism that protects us against bacterial infections in the lungs. The study is being published in the American Journal of Respiratory an ...

User comments : 0