title: [Novel type of signaling molecules: protein kinases covalently linked to ion channels].
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 Dictyostelium myosin heavy chain kinases. Here we cloned, sequenced and analyzed the tissue distribution of five new putative mammalian alpha-kinases: melanoma alpha-kinase, kidney alpha-kinase, heart alpha-kinase, skeletal muscle alpha-kinase, and lymphocyte alpha-kinase. All five are large proteins of more than 1000 amino acids with an alpha-kinase catalytic domain located at the very carboxyl-terminus. We expressed the catalytic domain of melanoma alpha-kinase in Escherichia coli, and found that it autophosphorylates on threonine residues, demonstrating that it is a genuine protein kinase. Unexpectedly, we found that the long amino-terminal portions of melanoma and kidney alpha-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 alpha-kinases, which represent a novel type of signaling molecule, are involved in the regulation of Ca2+ influx in mammalian cells.
authors.affiliation: Department of Pharmacology, University of Medicine & Dentistry of New Jersey, Robert Wood Johnson Medical School, Piscataway, NJ 08854, USA.
authors.forename: L V
authors.initials: LV
authors.lastname: Riazanova
authors.forename: K S
authors.initials: KS
authors.lastname: Pavur
authors.forename: A N
authors.initials: AN
authors.lastname: Petrov
authors.forename: M V
authors.initials: MV
authors.lastname: Dorovkov
authors.forename: A G
authors.initials: AG
authors.lastname: Riazanov
mesh_terms: D000818:Animals; D002118:Calcium / Q000502:physiology; D004023:Dictyostelium; D004926:Escherichia coli; D006801:Humans; D007473:Ion Channels; D011494:Protein Kinases; D015398:Signal Transduction
chemical_list: D007473:Ion Channels; D011494:Protein Kinases; D002118:Calcium