Novel type of signaling molecules: Protein kinases covalently linked with ion channels

L. V. Ryazanova, K. S. Pavur, A. N. Petrov, M. V. Dorovkov, A. G. Ryazanov

Research output: Contribution to journalArticlepeer-review

20 Scopus citations

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 α-kinases: melanoma α-kinase, kidney α-kinase, heart α-kinase, skeletal muscle α-kinase, and lymphocyte α-kinase. All five are large proteins of more than 1000 amino acids with an α-kinase catalytic domain located in the carboxyterminal part. We expressed the catalytic domain of melanoma α-kinase in Escherichia coil, 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 α-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 α-kinases, which represent a novel type of signaling molecule, are involved in the regulation of Ca2+ influx in mammalian cells.

Original languageEnglish (US)
Pages (from-to)271-283
Number of pages13
JournalMolecular Biology
Volume35
Issue number2
DOIs
StatePublished - Mar 2001

All Science Journal Classification (ASJC) codes

  • Biophysics
  • Structural Biology

Keywords

  • Alpha-kinases
  • Calcium channels
  • Protein kinases
  • TRP channels
  • eEF-2 kinase

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