Ca2+/calmodulin-dependent protein kinase cascade in Caenorhabditis elegans. Implication in transcriptional activation

Koh Eto, Naomi Takahashi, Yoshishige Kimura, Yasuhiko Masuho, Ken Ichi Arai, Masa Aki Muramatsu, Hiroshi Tokumitsu

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43 Citations (Scopus)


We have recently demonstrated that Caenorhabditis elegans Ca2+/calmodulin-dependent protein kinase kinase (CeCaM-KK) can activate mammalian CaM-kinase IV in vitro (Tokumitsu, H., Takahashi, N., Eto, K., Yano, S., Soderling, T.R., and Muramatsu, M. (1999) J. Biol. Chem. 274, 15803-15810). In the present study, we have identified and cloned a target CaM-kinase for CaM-KK in C. elegans, CeCaM-kinase I (CeCaM-KI), which has approximately 60% identity to mammalian CaM-KI. CeCaM-KI has 348 amino acid residues with an apparent molecular mass of 40 kDa, which is activated by CeCaM-KK through phosphorylation of Thr179 in a Ca2+/CaM-dependent manner, resulting in a 30-fold decrease in the K(m) of CeCaM-KI for its peptide substrate. Unlike mammalian CaM-KI, CeCaM-KI is mainly localized in the nucleus of transfected cells because the NH2-terminal six residues (2pLFKRR7) contain a functional nuclear localization signal. We have also demonstrated that CeCaM-KK and CeCaM-KI reconstituted a signaling pathway that mediates Ca2+-dependent phosphorylation of cAMP response element- binding protein (CREB) and CRE-dependent transcriptional activation in transfected cells, consistent with nuclear localization of CeCaM-KI. These results suggest that the CaM-KK/CaM-KI cascade is conserved in C. elegans and is functionally operated both in vitro and in intact cells, and it may be involved in Ca2+-dependent nuclear events such as transcriptional activation through phosphorylation of CREB.

Original languageEnglish
Pages (from-to)22556-22562
Number of pages7
JournalJournal of Biological Chemistry
Issue number32
Publication statusPublished - Aug 6 1999
Externally publishedYes

ASJC Scopus subject areas

  • Biochemistry
  • Molecular Biology
  • Cell Biology


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