title: TRPC3 amplifies B-cell receptor-induced ERK signalling via protein kinase D-dependent Rap1 activation.
abstract: Sustained activation of extracellular-signal-regulated kinase (ERK) has an important role in the decision regarding the cell fate of B-lymphocytes. Recently, we demonstrated that the diacylglycerol-activated non-selective cation channel canonical transient receptor potential 3 (TRPC3) is required for the sustained ERK activation induced by the B-cell receptor. However, the signalling mechanism underlying TRPC3-mediated ERK activation remains elusive. In the present study, we have shown that TRPC3 mediates Ca(2+) influx to sustain activation of protein kinase D (PKD) in a protein kinase C-dependent manner in DT40 B-lymphocytes. The later phase of ERK activation depends on the small G-protein Rap1, known as a downstream target of PKD, whereas the earlier phase of ERK activation depends on the Ras protein. It is of interest that sustained ERK phosphorylation is required for the full induction of the immediate early gene Egr-1 (early growth response 1). These results suggest that TRPC3 reorganizes the BCR signalling complex by switching the subtype of small G-proteins to sustain ERK activation in B-lymphocytes.
authors.affiliation: Division of Cardiocirculatory Signaling, Okazaki Institute for Integrative Bioscience (National Institute for Physiological Sciences), National Institutes of Natural Sciences, 5-1 Higashiyama, Myodaiji-cho, Okazaki, Aichi 444-8787, Japan SOKENDAI (School of Life Science, The Graduate University for Advanced Studies), Graduate School of Pharmaceutical Sciences, Kyushu University, Fukuoka 812-8582, Japan.
authors.forename: Takuro
authors.initials: T
authors.lastname: Numaga-Tomita
authors.affiliation: Division of Cardiocirculatory Signaling, Okazaki Institute for Integrative Bioscience (National Institute for Physiological Sciences), National Institutes of Natural Sciences, 5-1 Higashiyama, Myodaiji-cho, Okazaki, Aichi 444-8787, Japan SOKENDAI (School of Life Science, The Graduate University for Advanced Studies), Graduate School of Pharmaceutical Sciences, Kyushu University, Fukuoka 812-8582, Japan PRESTO, JST, 4-1-8 Honcho, Kawaguchi, Saitama 332-0012, Japan nishida@nips.ac.jp mori@sbchem.kyoto-u.ac.jp.
authors.forename: Motohiro
authors.initials: M
authors.lastname: Nishida
authors.affiliation: National Institute of Environmental Health Sciences, National Institutes of Health (NIH), 2233, Research Triangle Park, NC 27709, U.S.A.
authors.forename: James W
authors.initials: JW
authors.lastname: Putney
authors.affiliation: Laboratory of Molecular Biology, Department of Synthetic and Biological Chemistry, Graduate School of Engineering, Kyoto University, Kyoto University Katsura campus, Nishikyo-ku, Kyoto 615-8510, Japan nishida@nips.ac.jp mori@sbchem.kyoto-u.ac.jp.
authors.forename: Yasuo
authors.initials: Y
authors.lastname: Mori
mesh_terms: D000818:Animals; D001402:B-Lymphocytes / Q000378:metabolism*; D002460:Cell Line; D002645:Chickens; D020935:MAP Kinase Signaling System / Q000502:physiology*; D011493:Protein Kinase C / Q000378:metabolism*; D050052:TRPC Cation Channels / Q000096:biosynthesis*; D020827:rap1 GTP-Binding Proteins / Q000378:metabolism*
chemical_list: D050052:TRPC Cation Channels; C104603:TRPC3 cation channel; C089212:protein kinase D; D011493:Protein Kinase C; D020827:rap1 GTP-Binding Proteins
keywords: B-lymphocytes; Ca2+ signalling; ERK; Egr-1; Rap1; TRP channel