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 Dictyostelium myosin heavy chain kinases. Here we cloned, sequenced and analyzed the tissue distribution of five new putative mammalian a-kinases: melanoma a-kinase, kidney oc-kinase, heart oc-kinase, skeletal muscle a-kinase, and lymphocyte oc-kinase. All five are large proteins of more than 1000 amino acids with an a-kinase catalytic domain located at the very carboxylterminus. We expressed the catalytic domain of melanoma a-kinase in Escherichia coli, and found that it autophosphorylates on threonine residues, demonstrating that it is a genuine protein kinase. Unexpectedly, we found that me long ammo-terminal portions of melanoma and kidney a-kinases represent new members of the transient receptor potential (TRP) ion channel family, which are implicated in the mediation of capacitative Ca2+ entry in nonexcitable mammalian cells. This suggests that melanoma and kidney a-kinases, which represent a novel type of signaling molecule, are involved in the regulation of Ca2+ influx in mammalian cells.
|Original language||English (US)|
|Number of pages||12|
|State||Published - 2001|
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