Researchers have discovered a new protein component of cell-signaling pathways that does double dutyacting as both an ion channel that controls calcium entry into cells and as an enzyme that activates itself and perhaps other proteins. While they do not yet know how the protein is activated, they have found that it is present in many tissues, including brain, kidney and heart. The researchers speculate that the protein might be involved in cell proliferation or cell death, making it a potential new drug target.

Howard Hughes Medical Institute investigator David E. Clapham and colleagues Loren W. Runnels and Lixia Yue at Children's Hospital in Boston and Harvard Medical School reported on the new protein in an article published online on January 19, 2001, on Sciencexpress, the Web-based counterpart of Science magazine.

The new protein, called transient receptor protein-phospholipase C-interacting kinase (TRP-PLIK), is a member of a family of ion channel proteins that controls the entry of calcium into the cell, said Clapham. "The TRP channels are important to cell regulation because calcium is the most tightly controlled ion in biology," he said. "The concentration of calcium outside the cell is about twenty-thousand-fold that inside the cell. Its entry is controlled so precisely because it triggers many cell processes, from muscle contraction to the firing of neurons." Despite their importance, though, little is known about how TRP channels are activated, he said.

Furthermore, it appears that TRP-PLIK is unique among TRP channels, said Clapham, because it is both a calcium ion channel and a kinase, an enzyme that activates other proteins by phosphorylatingor adding a phosphate to them. "The most exciting part of this finding for us was that TRP-PLIK is bi-functional," he said. "It contains a domain whose opening and closing acts as a gate for calcium and a do
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Contact: Jim Keeley
keeleyj@hhmi.org
301-215-8858
Howard Hughes Medical Institute
18-Jan-2001