RalGDS-like factor (Rlf) is a novel Ras and Rap 1A-associating protein

R M Wolthuis1, B Bauer, L J van 't Veer

  • 1Laboratory for Physiological Chemistry, Utrecht University, The Netherlands.

Oncogene
|July 18, 1996
PubMed

Insights

Researchers identified a novel Rap 1A-interacting protein, Rlf, which acts as a Ral guanine nucleotide dissociation stimulator-like factor. Rlf directly binds to the GTP-bound forms of Ras and Rap 1A, suggesting it functions as an effector for these small GTPases.

Area of Science:

  • Molecular Biology
  • Cell Signaling
  • Oncogenesis

Background:

  • The small GTPase Rap 1A, related to Ras, can reverse Ras-induced oncogenic transformation.
  • Understanding Rap 1A and Ras signaling pathways is crucial for cancer research.

Purpose of the Study:

  • To identify novel proteins that interact with Rap 1A.
  • To characterize the function and binding properties of a newly discovered Rap 1A-interacting protein.

Main Methods:

  • Yeast two-hybrid screening of a mouse embryonic cDNA library.
  • In vitro binding assays to determine protein-protein interactions and binding affinities.

Main Results:

  • A novel Rap 1A-interacting protein, designated Rlf (RalGDS-like factor), was identified.
  • Rlf shares homology with Ral guanine nucleotide dissociation stimulator (RalGDS) and contains a Cdc25-homology domain.
  • Rlf specifically binds to the GTP-bound forms of Ras and Rap 1A with high affinity, but not their GDP-bound forms.

Conclusions:

  • Rlf is a putative effector for Ras and Rap 1A.
  • The discovery of Rlf provides new insights into the regulatory mechanisms of Ras and Rap 1A signaling pathways.

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:
The Ras Gene02:38

The Ras Gene

The Ras-gene-encoded proteins are regulators of signaling pathways controlling cell proliferation, differentiation, or cell survival. The Ras-gene family in humans constitutes three primary members—the HRas, NRas, and KRas. These genes code for four functionally distinct yet closely related proteins—the HRas, NRas, KRas4A, and KRas4B. The involvement of mutant Ras genes in human cancer was first discovered in 1982 and is among the most common causes of human tumorigenesis.
Ras is a superfamily...
MAPK Signaling Cascades01:07

MAPK Signaling Cascades

Mitogen-activated protein kinase, or MAPK pathway, activates three sequential kinases to regulate cellular responses such as proliferation, differentiation, survival, and apoptosis. The canonical MAPK pathway starts with a mitogen or growth factor binding to an RTK. The activated RTKs stimulate Ras, which recruits Raf or MAP3 Kinase (MAPKKK), the first kinase of the MAPK signaling cascade. Raf further phosphorylates and activates MEK or MAP2 Kinases (MAPKK), which in turn phosphorylates MAP...
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...