Roles of 14-3-3 and calmodulin binding in subcellular localization and function of the small G-protein Rem2

Biochem J. 2005 Aug 15;390(Pt 1):67-75. doi: 10.1042/BJ20050414.


kir/Gem, Rad, Rem and Rem2 comprise the RGK (Rad/Gem/kir) family of Ras-related small G-proteins. Two important functions of RGK proteins are the regulation of the VDCC (voltage-dependent Ca2+ channel) activity and cell-shape remodelling. RGK proteins interact with 14-3-3 and CaM (calmodulin), but their role on RGK protein function is poorly understood. In contrast with the other RGK family members, Rem2 has been reported to bind neither 14-3-3 nor induce membrane extensions. Furthermore, although Rem2 inhibits VDCC activity, it does not prevent cell-surface transport of Ca2+ channels as has been shown for kir/Gem. In the present study, we re-examined the functions of Rem2 and its interaction with 14-3-3 and CaM. We show that Rem2 in fact does interact with 14-3-3 and CaM and induces dendrite-like extensions in COS cells. 14-3-3, together with CaM, regulates the subcellular distribution of Rem2 between the cytoplasm and the nucleus. Rem2 also interacts with the beta-subunits of VDCCs in a GTP-dependent fashion and inhibits Ca2+ channel activity by blocking the alpha-subunit expression at the cell surface. Thus Rem2 shares many previously unrecognized features with the other RGK family members.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • 14-3-3 Proteins / chemistry*
  • 14-3-3 Proteins / physiology
  • Amino Acid Sequence
  • Animals
  • Binding Sites
  • Biological Transport, Active
  • Calcium Channels / physiology
  • Calmodulin / chemistry*
  • Calmodulin / physiology
  • Cell Line
  • Cell Shape / physiology
  • Gene Expression Regulation / physiology
  • Humans
  • Ion Transport
  • Monomeric GTP-Binding Proteins / chemistry*
  • Monomeric GTP-Binding Proteins / physiology*
  • Protein Binding
  • Protein Isoforms
  • Protein Subunits
  • Sequence Homology, Amino Acid


  • 14-3-3 Proteins
  • Calcium Channels
  • Calmodulin
  • Protein Isoforms
  • Protein Subunits
  • Monomeric GTP-Binding Proteins
  • Rem2 protein, rat