The polybasic region of Ras and Rho family small GTPases: a regulator of protein interactions and membrane association and a site of nuclear localization signal sequences

Cell Signal. 2003 Dec;15(12):1071-80. doi: 10.1016/s0898-6568(03)00098-6.


Many small GTPases in the Ras and Rho families have a C-terminal polybasic region (PBR) comprised of multiple lysines or arginines. The PBR controls diverse functions of these small GTPases, including their ability to associate with membranes, interact with specific proteins, and localize in subcellular compartments. Different signaling pathways mediated by Ras and Rho family members may converge when the small GTPases are directed by their PBRs to shared binding sites in specific proteins or at cell membranes. The PBR promotes the interactions of small GTPases with SmgGDS, which is a nucleocytoplasmic shuttling protein that stimulates guanine nucleotide exchange by small GTPases. The PBR of Rac1 was recently found to have a functional nuclear localization signal (NLS) sequence, which enhances the nuclear accumulation of protein complexes containing SmgGDS and Rac1. Sequence analysis demonstrates that canonical NLS sequences (K-K/R-x-K/R) are present in the PBRs of additional Ras and Rho family members, and are evolutionarily conserved across several phyla. These findings suggest that the PBR regulates the nucleocytoplasmic shuttling of some Ras and Rho family members when they are in protein complexes that are too large to diffuse through nuclear pores. These diverse functions of the PBR indicate its critical role in signaling by Ras and Rho family GTPases.

Publication types

  • Research Support, Non-U.S. Gov't
  • Research Support, U.S. Gov't, P.H.S.
  • Review

MeSH terms

  • Active Transport, Cell Nucleus / physiology
  • Amino Acid Sequence
  • Animals
  • Cell Membrane / metabolism
  • Evolution, Molecular
  • Guanine Nucleotide Exchange Factors / metabolism
  • Humans
  • Intracellular Membranes / metabolism
  • Membranes / metabolism*
  • Models, Biological
  • Molecular Sequence Data
  • Monomeric GTP-Binding Proteins / genetics
  • Monomeric GTP-Binding Proteins / metabolism*
  • Nuclear Localization Signals / physiology*
  • Protein Binding
  • Protein Isoforms / metabolism
  • Protein Prenylation
  • Protein Transport / physiology
  • Sequence Homology, Amino Acid
  • alpha Karyopherins / metabolism
  • rho GTP-Binding Proteins / genetics
  • rho GTP-Binding Proteins / metabolism*


  • Guanine Nucleotide Exchange Factors
  • Nuclear Localization Signals
  • Protein Isoforms
  • RAP1GDS1 protein, human
  • alpha Karyopherins
  • Monomeric GTP-Binding Proteins
  • rho GTP-Binding Proteins