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Decision making at the cellular level

It's a wonder cells make it through the day with the barrage of cues and messages they receive and transmit to direct the most basic and necessary functions of life. Such cell communication, or signal transduction, was at least thought to be an "automatic" cascade of biochemical events.

Now, however, a study reported in a recent issue of Nature by Johns Hopkins and Harvard scientists has found that even before a message makes it through the outer cell membrane to the inner nucleus, the cell is busy activating a molecular switch to guide how the message will be delivered in the first place.

"Our results add a layer of complexity to understanding how messages are communicated by cells," says Mark Donowitz, M.D., professor of medicine at Hopkins and a co-author of the study in the June 20 issue. "But by the same token, the new layer offers an exciting new aspect of cellular circuitry that could lead to potential therapies for many serious disorders," he says.

"This extra step in cell signaling actually lets the cell figure out how it's going to communicate what it needs to," says Donowitz. "Without this switchboard system, the cell would go crazy and overload because every stimulus that passed by would be forwarded to its interior."

The two most common cellular signals are calcium and cyclic adenosine monophosphate, or cAMP. They are sometimes known as "second messengers" because they intercept messages from receptors on the cell surface and relay them to proteins within the cell, altering their shape and thus their behavior and that of the cell at large.

Donowitz and colleagues showed that a cell decides which signal to use, calcium or cAMP, by the presence or absence of a specific protein called sodium/hydrogen exchanger regulatory factor 2, or NHERF2. Specifically, their experiments tested how the receptor for parathyroid hormone, and for parathyroid hormone-related protein (also a hormone), on the cell surface signals the
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Contact: Trent Stockton
tstockt1@jhmi.edu
410-955-8665
Johns Hopkins Medical Institutions
25-Jun-2002


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