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TRPM7 is a ubiquitously expressed protein that has the exceptional feature of being both a functional ion channel and kinase (1). In contrast to many other TRP channels, which are activated through receptors that couple to phospholipase C (PLC), our studies have shown that receptor-mediated activation of PLC dramatically inhibits TRPM7’s channel activity (2). These experiments reveal that phosphatidylinositol 4,5-bisphosphate (PIP2), a substrate of PLC, potently gates the channel. We speculate that there also may be a role for phosphatidylinositol phosphate kinases in regulating channel activity.
Although much has been learned about how the channel activity of TRPM7 is controlled, many questions still remain unanswered. One of the goals of the Runnels’ lab is to identify the signaling pathways that regulate the activation of the protein’s channel and kinase activities. In addition, our group is working towards the identification of substrates for the TRPM7 kinase. And finally, we want to understand why nature chose to endow this ion channel with its own kinase domain and what may be the physiological role of this truly unique bifunctional protein.
1. Runnels, L. W., Yue, L. & Clapham, D. E. TRP-PLIK, a Bifunctional Protein with Kinase and Ion Channel Activities. Science 291, 1043-1047 (2001).
2. Runnels, L. W., Yue, L. & Clapham, D. E. The TRPM7 channel is inactivated by PIP2 hydrolysis. Nature Cell Biol. 4, 329-336 (2002).