Related Experiment Video

Updated: Mar 20, 2026

Affinity Precipitation of Active Rho-GEFs Using a GST-tagged Mutant Rho Protein GST-RhoAG17A from Epithelial Cell Lysates
11:28

Affinity Precipitation of Active Rho-GEFs Using a GST-tagged Mutant Rho Protein GST-RhoAG17A from Epithelial Cell Lysates

Published on: March 31, 2012

17.0K

Coevolution of RAC Small GTPases and their Regulators GEF Proteins

Alejandro Jiménez-Sánchez1

  • 1Cancer Research UK Cambridge Institute, University of Cambridge, Li Ka Shing Centre, Cambridge, UK.; Previously at Department of Biology, University of York, York, UK.

Evolutionary Bioinformatics Online
|May 27, 2016
PubMed

Insights

RAC proteins, crucial for cell processes and cancer, are regulated by unrelated DOCK and DBL guanine nucleotide exchange factors (GEFs). Phylogenetic and coevolution analyses reveal conserved RAC-DOCK and RAC-DBL interactions, despite DBL protein divergence.

Area of Science:

  • Molecular Biology
  • Evolutionary Biology
  • Biochemistry

Background:

  • RAC proteins are small GTPases essential for eukaryotic cellular functions, with deregulation linked to cancer.
  • Activation of RAC proteins is mediated by guanine nucleotide exchange factors (GEFs) from the DOCK and DBL protein families.
  • Despite performing the same function on RAC proteins, DOCK and DBL GEF families are evolutionarily distinct.

Purpose of the Study:

  • To investigate the evolutionary relationship and coevolutionary patterns between RAC proteins and their GEFs (DOCK and DBL families).
  • To understand how evolutionarily unrelated protein families can perform the same biochemical function.

Main Methods:

  • Phylogenetic analyses were conducted on the RAC, DBL, and DOCK protein families.
  • Interaction patterns suggesting coevolution were searched for within these families.
  • Correlation analyses of phylogenetic distances and covariation analyses of interacting residues were performed.

Main Results:

  • RAC and DOCK proteins are highly conserved across eukaryotes, whereas DBL proteins exhibit significant divergence.
  • Significant coevolution rates were detected for both RAC-DOCK and RAC-DBL interactions.
  • Covariation analyses indicated coordinated evolutionary changes in interacting domains.

Conclusions:

  • The findings suggest a coevolutionary process between RAC proteins and both DOCK and DBL GEF families, despite their distinct evolutionary origins.
  • This coevolution highlights conserved functional interactions and regulatory mechanisms despite structural divergence in GEF families.
  • Understanding these interactions provides insights into the regulation of RAC GTPases in cellular processes and cancer.
Keywords:
CoevolutionDBLDOCKGEF proteinsRACSmall GTPases

More Related Videos

Comparing the Affinity of GTPase-binding Proteins using Competition Assays10:37

Comparing the Affinity of GTPase-binding Proteins using Competition Assays

Published on: October 8, 2015

9.7K
Detection of Small GTPase Prenylation and GTP Binding Using Membrane Fractionation and GTPase-linked Immunosorbent Assay13:51

Detection of Small GTPase Prenylation and GTP Binding Using Membrane Fractionation and GTPase-linked Immunosorbent Assay

Published on: November 11, 2018

10.4K

Related Concept Videos

Small GTPases - Ras and Rho01:24

Small GTPases - Ras and Rho

Ras and Rho are small monomeric GTPases that act downstream of receptor tyrosine kinase (RTK) and regulate various cellular processes. These GTPases switch between active and inactive states by binding to guanine nucleotides.
Three regulatory proteins control their activity:
5.7K
Rab Proteins01:14

Rab Proteins

Rab proteins constitute the largest family of monomeric GTPases, of which 70 members are present in humans. Rab proteins and their effectors regulate consecutive stages of vesicle transport such as vesicle transport, docking, and fusion to the correct recipient membrane.
Rab proteins switch between a cytosolic, GDP-bound inactive state and a membrane-anchored, GTP-bound active state. By themselves, Rabs show slow rates of GDP/GTP exchange and GTP hydrolysis. Thus, Rab proteins are considered...
5.4K
GTPases and their Regulation02:14

GTPases and their Regulation

Guanine nucleotide-binding proteins (G-proteins), also known as GTPases, are a superfamily of proteins that regulate many cellular processes, such as cell signaling, vesicular transport, and the regulation of cell shape and motility. Mutation or dysfunction of these proteins can lead to disease. There are around 40,000 known G-proteins that can broadly be classified into two groups ‒  small G-proteins consisting of a single domain and large multi-domain G-proteins.
Large G-proteins,...
10.2K
GTPases and their Regulation02:14

GTPases and their Regulation

3.2K
Cell Polarization by Rho Proteins01:21

Cell Polarization by Rho Proteins

Cell polarity is the asymmetric distribution of cellular and membrane components, making one side of the cell different from the other. This polarity is essential to many processes such as embryogenesis, axon migration, glucose transport across epithelial cells, and directional cell migration. A migrating cell responds to intracellular or extracellular signals via molecular cascades that reorganize the actin cytoskeleton to establish this polarity. In these cells, the Rho family proteins Cdc42,...
4.0K
Activation and Inactivation of G Proteins01:22

Activation and Inactivation of G Proteins

Heterotrimeric G proteins are guanine nucleotide-binding proteins. As the name suggests, heterotrimeric G proteins are composed of three subunits: alpha, beta, and gamma. They remain GDP-bound or GTP-bound inside the cells and switch between inactive/active states. The Gα subunit possesses the nucleotide-binding pocket that binds guanine nucleotides and switches between GDP or GTP-bound states. In contrast, the Gꞵ and Gγ subunits are always bound together with high...
12.3K