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Novel protein kinases and signal transductionWe have recently discovered a new class of protein kinases -- alpha-kinases.
Alpha-kinases play an important role in the control of protein synthesis. cell
growth and differentiation. One of the alpha-kinases. elongation factor-2
kinase (eEF2 kinase) can regulate the global rate of protein synthesis and is
implicated in cancer and aging. Two other alpha-kinases that we recently
identified represent a novel type of signaling molecule that consists of a
protein kinase fused to an ion channel (channel-kinases). Why would a kinase and
an ion channel be contained in one molecule? Is the channel activity controlled
by the kinase. or is the kinase controlled by ion flow through the channel? What
is the physiological role of channel-kinases and other alpha-kinases? We are
using molecular biological. cell biological. and bioinformatic approaches as
well as transgenic animals to investigate the structure and function of these
fascinating molecules. Selected PublicationsClark K, Middelbeek J, Lasonder E, Dulyaninova NG, Morrice NA, Ryazanov AG, Bresnick AR, Figdor CG, van Leeuwen FN. (2008) TRPM7 regulates myosin IIA filament stability and protein localization by heavy chain phosphorylation. J Mol Biol. 378(4):788-801. Hars ES, Qi H, Ryazanov AG, Jin S, Cai L, Hu C, Liu LF. (2007) Autophagy regulates ageing in C. elegans. Autophagy. 3(2):93-5. Clark K. Langeslag M. van Leeuwen B. Ran L. Ryazanov AG. Figdor CG. Moolenaar WH. Jalink K. van Leeuwen FN. (2006) TRPM7. a novel regulator of actomyosin contractility and cell adhesion. EMBO J. 25(2):290-301. Schmitz C. Dorovkov MV. Zhao X. Davenport BJ. Ryazanov AG. Perraud AL. (2005) The channel kinases TRPM6 and TRPM7 are functionally nonredundant. J Biol Chem. 280(45):37763-71. Hermosura MC. Nayakanti H. Dorovkov MV. Calderon FR. Ryazanov AG. Haymer DS. Garruto RM. (2005) A TRPM7 variant shows altered sensitivity to magnesium that may contribute to the pathogenesis of two Guamanian neurodegenerative disorders. Proc Natl Acad Sci U S A. 102(32):11510-5. Heine M. Cramm-Behrens CI. Ansari A. Chu HP. Ryazanov AG. Naim HY. Jacob R. (2005) Alpha-kinase 1. a new component in apical protein transport. J Biol Chem. 280(27):25637-43. Dorovkov MV. Ryazanov AG. (2004) Phosphorylation of annexin I by TRPM7 channel-kinase. J Biol Chem. 279(49):50643-6. Drennan. D. and Ryazanov. A.G. (2003) Alpha-kinases: analysis of the family and comparison with conventional protein kinases. Progress in Biophysics and Molecular Biology. in press. Ryazanova. L.V.. Dorovkov. M.V.. Ansari. A.. and Ryazanov. A.G. (2003) Characterization of the protein kinase activity of TRPM7/ChaK1. a protein kinase fused to TRP ion channel. J. Biol. Chem. 279(5):3708-16. Dorovkov M.V.. Pavur K.S.. Petrov A.N.. and Ryazanov A.G. (2002) Regulation of elongation factor-2 kinase by pH. Biochemistry 41:13444-13450. Ryazanov. A.G.. and Nefsky. B.S. (2002) Protein turnover plays a key role in aging. Mech. Ageing Dev. 123: 207-213. Ryazanov. A.G. (2002) Elongation factor-2 kinase and its newly discovered relatives. FEBS letters 514: 26-29. Ryazanova. L.V.. Pavur. K.S.. Petrov. A.N.. Dorovkov. M.V. and Ryazanov. A.G. (2001) Novel type of signaling molecules: protein kinases covalently linked with ion channels. Mol. Biol. 35: 271-283. Alberdi F. Dadone J. Ryazanov AG. Isenberg DA. Ravirajan C. Reichlin M (2001) Cross-reaction of lupus anti-dsDNA antibodies with protein translation factor EF-2. Clin. Immunol. 98: 293-300. Pavur. K.S.. Petrov. A.N.. and Ryazanov. A.G. (2000) Mapping the functional domains of elongation factor-2 kinase. Biochemistry 39: 12216-12224. |
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