Calcium/Calmodulin-Dependent Protein Kinase Type IV Is a Target Gene of the Wnt/beta-Catenin Signaling Pathway


ARRAZOLA M. S., VARELA-NALLAR L., COLOMBRES M., TOLEDO E. M., CRUZAT F., PAVEZ L., ...Daha Fazla

JOURNAL OF CELLULAR PHYSIOLOGY, cilt.221, sa.3, ss.658-667, 2009 (SCI-Expanded) identifier identifier identifier

  • Yayın Türü: Makale / Tam Makale
  • Cilt numarası: 221 Sayı: 3
  • Basım Tarihi: 2009
  • Doi Numarası: 10.1002/jcp.21902
  • Dergi Adı: JOURNAL OF CELLULAR PHYSIOLOGY
  • Derginin Tarandığı İndeksler: Science Citation Index Expanded (SCI-EXPANDED), Scopus
  • Sayfa Sayıları: ss.658-667
  • İstanbul Üniversitesi Adresli: Hayır

Özet

Calcium/calmodulin-dependent protein kinase IV (CaMKIV) plays a key role in the regulation of calcium-dependent gene expression. The expression of CaMKIV and the activation of CREB regulated genes are involved in memory and neuronal survival. We report here that: (a) a bioinformatic analysis of 15,476 promoters of the human genome predicted several Wnt target genes, being CaMKIV a very interesting candidate; (b) CaMKIV promoter contains TCF/LEF transcription motifs similar to those present in Wnt target genes; (c) biochemical studies indicate that lithium and the canonical ligand Wnt-3a induce CaMKIV mRNA and protein expression levels in rat hippocampal neurons as well as CaMKIV promoter activity; (d) treatment of hippocampal neurons with Wnt-3a increases the binding of beta-catenin to the CaMKIV promoter: (e) In vivo activation of the Wnt signaling improve spatial memory impairment and restores the expression of CaMKIV in a mice double transgenic model for Alzheimer's disease which shows decreased levels of the kinase. We conclude that CaMKIV is regulated by the Wnt signaling pathway and that its expression could play a role in the neuroprotective function of the Wnt signaling against the Alzheimer's amyloid peptide. J. Cell. Physiol. 221: 658-667, 2009. (C) 2009 Wiley-Liss, Inc.