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Scientists map signaling molecule crucial to survival, disease

A chemical sleight of hand by UCSF scientists has pinpointed for the first time where small molecules called phosphates bind to proteins in cells, allowing them to send signals and giving organisms a way to adapt to rapidly changing conditions.

Diabetes, hypertension and many cancers arise when these simple molecules bind incorrectly or not at all. Mapping their location on proteins should allow researchers to block aberrant binding and treat disease, the scientists say.

The addition of phosphates is nature's dominant way of transferring information within and between cells, the researchers say. One third of all proteins in the human body carry phosphates; some proteins are studded with as many as 50 of the small molecular add-ons. In essence, the phosphate addition, known as phosphorylation, induces a protein to send a signal to a second protein. Such signals are vital for survival, allowing cells to respond to changes in their environment by, for example, regulating the production and transport of hormones, nutrients, and the like.

But the common signaling system is vulnerable to sabotage. Many cancer cells rely on aberrant phosphorylation to avoid a normal death, either by carrying more phosphate bonds than normal or making excess proteins with the normal number of phosphates, the scientists say. The opposite can also be life-threatening: Insufficient phosphorylation can cause diseases such as diabetes by dampening the cellular effects of insulin.

"This finding will allow us for the first time to quickly identify all the changes in protein phosphorylation that occur in a cell," said Kevan Shokat, PhD, professor of cellular and molecular pharmacology at UCSF and also professor of chemistry at UC Berkeley. "Since phosphorylation controls so many biological processes and is involved in so many diseases, mapping the sites where it takes place will identify new therapeutic targets."

Shokat is senior author on a paper re
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Contact: Wallace Ravven
wravven@pubaff.ucsf.edu
415-502-1332
University of California - San Francisco
20-Aug-2003


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