The RGK family of GTP-binding proteins: regulators of voltage-dependent calcium channels and cytoskeleton remodeling

Cell Signal. 2008 Feb;20(2):292-300. doi: 10.1016/j.cellsig.2007.10.028. Epub 2007 Nov 6.


RGK proteins constitute a novel subfamily of small Ras-related proteins that function as potent inhibitors of voltage-dependent (VDCC) Ca(2+) channels and regulators of actin cytoskeletal dynamics. Within the larger Ras superfamily, RGK proteins have distinct regulatory and structural characteristics, including nonconservative amino acid substitutions within regions known to participate in nucleotide binding and hydrolysis and a C-terminal extension that contains conserved regulatory sites which control both subcellular localization and function. RGK GTPases interact with the VDCC beta-subunit (Ca(V)beta) and inhibit Rho/Rho kinase signaling to regulate VDCC activity and the cytoskeleton respectively. Binding of both calmodulin and 14-3-3 to RGK proteins, and regulation by phosphorylation controls cellular trafficking and the downstream signaling of RGK proteins, suggesting that a complex interplay between interacting protein factors and trafficking contribute to their regulation.

Publication types

  • Research Support, N.I.H., Extramural
  • Research Support, Non-U.S. Gov't
  • Review

MeSH terms

  • Amino Acid Sequence
  • Animals
  • Calcium Channels / metabolism*
  • Cytoskeleton / metabolism*
  • GTP-Binding Proteins / chemistry
  • GTP-Binding Proteins / genetics
  • GTP-Binding Proteins / metabolism*
  • Humans
  • Molecular Sequence Data
  • Signal Transduction
  • rho GTP-Binding Proteins / metabolism


  • Calcium Channels
  • GTP-Binding Proteins
  • rho GTP-Binding Proteins