Molecular identification and characterization of a family of kinases with homology to Ca2+/calmodulin-dependent protein kinases I/IV

Shogo Ohmae, Sayaka Takemoto-Kimura, Michiko Okamura, Aki Adachi-Morishima, Mio Nonaka, Toshimitsu Fuse, Satoshi Kida, Masahiro Tanji, Tomoyuki Furuyashiki, Yoshiki Arakawa, Shuh Narumiya, Hiroyuki Okuno, Haruhiko Bito

Research output: Contribution to journalArticlepeer-review

22 Citations (Scopus)

Abstract

Despite the critical importance of Ca2+/calmodulin (CaM)-dependent protein kinase (CaMK) II signaling in neuroplasticity, only a limited amount of work has so far been available regarding the presence and significance of another predominant CaMK subfamily, the CaMKI/CaMKIV family, in the central nervous system. We here searched for kinases with a core catalytic structure similar to CaMKI and CaMKIV. We isolated full-length cDNAs encoding three mouse CaMKI/CaMKIV-related kinases, CLICK-I (CL1)/doublecortin and CaM kinase-Like (DCAMKL)1, CLICK-II (CL2)/DCAMKL2, and CLICK-I,II-related (CLr)/DCAMKL3, the kinase domains of which had an intermediate homology not only to CaMKI/CaMKIV but also to CaMKII. Furthermore, CL1, CL2, and CLr were highly expressed in the central nervous system, in a neuron-specific fashion. CL1α and CL1β were shorter isoforms of DCAMKL1, which lacked the doublecortin-like domain (Dx). In contrast, CL2α and CL2β contained a full N-terminal Dx, whereas CLr only possessed a partial and dysfunctional Dx. Interestingly, despite a large similarity in the kinase domain, CL1/CL2/CLr had an impact on CRE-dependent gene expression distinct from that of the related CaMKI/CaMKIV and CaMKII. Although these were previously shown to activate Ca2+/cAMP-response element-binding protein (CREB)-dependent transcription, we here show that CL1 and CL2 were unable to significantly phosphorylate CREB Ser-133 and rather inhibited CRE-dependent gene expression by a dominant mechanism that bypassed CREB and was mediated by phosphorylated TORC2.

Original languageEnglish
Pages (from-to)20427-20439
Number of pages13
JournalJournal of Biological Chemistry
Volume281
Issue number29
DOIs
Publication statusPublished - 2006 Jul 21
Externally publishedYes

ASJC Scopus subject areas

  • Biochemistry
  • Molecular Biology
  • Cell Biology

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