Happy accident answers cell signal controversy

June 27, 2012

(Phys.org) -- Using a new tool allowing proteins in a living cell to be manipulated in real time, researchers at Johns Hopkins have stumbled across the answer to a longstanding debate about where and how a certain protein is turned on in the cell. Reporting in the February 2012 issue of Nature Chemical Biology, scientists show that protein kinase A is also activated in the nucleus rather than inside the cell’s body, a challenge to traditional beliefs.

“People have been wondering about nuclear PKA and [the answer] clicked when we saw our results,” says Jin Zhang, Ph.D, associate professor of pharmacology at Johns Hopkins. For the most part, those in the field believe that PKA is activated in the cell’s cytoplasm, but there is conflicting evidence suggesting it could also be present in the . Zhang says the answer to the debate clicked for her team when a cell biology technique they were fine-tuning gavethem unusual results.

Zhang and her research team are looking for the best way to see what’s happening in live in . Most recently, they developed a new tool to manipulate the intricate molecular signals within the cell, allowing the researchers to stimulate cellular activities so experiments rely on their timing rather than the cells’. The technique enables the scientists to chemically activate a chain of signals at a precise location and specific time, all of it culminating in the activation of PKA. This causes changes in the cell that lead to a variety of outcomes, from altering metabolism to causing a muscle contraction.

Given the wide range of cellular outcomes possible upon trigger of this chain of signals, Zhang and her team knew they must test their tool under many conditions to see the many different possibilities. They began by stimulating the chain at the edge of the cell. They measured how quickly the signaling chain responded, and engineers collaborating with Zhang came up with a mathematical equation to model the speed of the message going from the cell membrane into the nucleus.

Next, they tested their tool closer to the center of the cell, activating molecules at the edge of the nucleus. They found the response was much faster than anticipated; the mathematical equation did not fit. Thinking about this inconsistency led the team to conclude that the only way to explain their findings was if PKA was activated inside the nucleus, contrary to the traditional understanding of PKA being located and activated outside the nucleus.

According to Zhang, PKA has always been thought to be activated outside the nucleus. Upon activation, it travels into the nucleus to turn on the cell’s response. Zhang’s data showed the signal from PKA activated at the cell’s edge is slow in reaching the inside of nucleus, so the only explanation for a fast response at the nucleus would be if another population of PKA was already there.

“We’re collecting information that shows PKA at the nucleus is functional, it’s not contamination and not background signal,” says Zhang. “These are real functional enzymes that can be activated.”

Zhang and her colleagues now aims to find out how PKA at the nucleus differs from traditional PKA. Without doubt, PKA plays a critical role in many cellular processes, says Zhang. This means that nuclear PKA could be a significant and, as yet, untapped source of information about cell function.

Authors on the paper include Vedangi Sample, Lisa M DiPilato, Qiang Ni and Jin Zhang of Johns Hopkins, and Jason H. Yang and Jeffrey J. Saucerman of University of Virginia.

Explore further: Researchers develop new tool to watch real-time chemical activity in cells

Related Stories

Study reveals the regulatory mechanism of key enzyme

September 20, 2007

Research conducted at the University of California, San Diego (UCSD) School of Medicine has shed new light on the structure and function of one of the key proteins in all mammalian cells, protein kinase A (PKA), an enzyme ...

The beat goes on with AKAP18

September 28, 2007

A protein, known as AKAP18, could help the heart to beat faster in response to adrenaline or noradrenaline, according to a study published online this week in EMBO reports.

New approach to treating breast and prostate cancers

February 9, 2010

In a new approach to developing treatments for breast cancer, prostate cancer and enlarged hearts, Loyola University Chicago Stritch School of Medicine researchers are zeroing in on a workhorse protein called RSK.

Recommended for you

New method developed for producing some metals

August 25, 2016

The MIT researchers were trying to develop a new battery, but it didn't work out that way. Instead, thanks to an unexpected finding in their lab tests, what they discovered was a whole new way of producing the metal antimony—and ...

Force triggers gene expression by stretching chromatin

August 26, 2016

How genes in our DNA are expressed into traits within a cell is a complicated mystery with many players, the main suspects being chemical. However, a new study by University of Illinois researchers and collaborators in China ...

New electrical energy storage material shows its power

August 24, 2016

A powerful new material developed by Northwestern University chemist William Dichtel and his research team could one day speed up the charging process of electric cars and help increase their driving range.

Bio-inspired tire design: Where the rubber meets the road

August 24, 2016

The fascination with the ability of geckos to scamper up smooth walls and hang upside down from improbable surfaces has entranced scientists at least as far back as Aristotle, who noted the reptile's remarkable feats in his ...


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.