Novel Type of Signaling Molecules: Protein Kinases Covalently Linked with Ion Channels |
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Authors: | Ryazanova L V Pavur K S Petrov A N Dorovkov M V Ryazanov A G |
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Institution: | (1) Department of Pharmacology, University of Medicine & Dentistry of New Jersey, Robert Wood Johnson Medical School, Piscataway, NJ 08854, USA |
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Abstract: | Recently we identified a new class of protein kinases with a novel type of catalytic domain structurally and evolutionarily unrelated to the conventional eukaryotic protein kinases. This new class, which we named alpha-kinases, is represented by eukaryotic elongation factor-2 kinase and the Dictyosteliummyosin heavy chain kinases. Here we cloned, sequenced, and analyzed the tissue distribution of five new putative mammalian -kinases: melanoma -kinase, kidney -kinase, heart -kinase, skeletal muscle -kinase, and lymphocyte -kinase. All five are large proteins of more than 1000 amino acids with an -kinase catalytic domain located in the carboxyterminal part. We expressed the catalytic domain of melanoma -kinase in Escherichia coli, and found that it autophosphorylates at threonine residues, demonstrating that it is a genuine protein kinase. Unexpectedly, we found that long aminoterminal portions of melanoma and kidney -kinases represent new members of the TRP ion channel family, which are thought to mediate the capacitative Ca2+entry in nonexcitable mammalian cells. This suggests that melanoma and kidney -kinases, which represent a novel type of signaling molecule, are involved in the regulation of Ca2+influx in mammalian cells. |
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Keywords: | alpha-kinases calcium channels eEF-2 kinase protein kinases TRP channels |
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