Identification of a novel ligand-receptor pair constitutively activated by ras oncogenes

Related Experiment Video

Updated: Oct 16, 2026

Identification of EGFR and RAS Inhibitors using Caenorhabditis elegans
08:12

Identification of EGFR and RAS Inhibitors using Caenorhabditis elegans

Published on: October 5, 2020

R Zhang1, Z Tan, P Liang

  • 1Vanderbilt-Ingram Cancer Center, Department of Cell Biology, School of Medicine, Vanderbilt University, Nashville, Tennessee 37232, USA.

The Journal of Biological Chemistry
|May 29, 2000
PubMed

Insights

Researchers discovered mob-5, a novel oncogenic Ras target gene crucial for cell growth. This gene, mob-5, may form an autocrine loop with its receptor, activated by Ras oncogenes, impacting cell transformation.

Area of Science:

  • Molecular Biology
  • Cellular Biology
  • Oncology

Background:

  • The Ras signaling pathway regulates critical cellular processes like growth and differentiation.
  • Specific genes controlled by Ras, particularly in oncogenic contexts, remain largely undefined.

Purpose of the Study:

  • To identify novel genes regulated by oncogenic Ras.
  • To investigate the role of these genes in cancer cell transformation.

Main Methods:

  • Differential display technique to identify novel gene expression.
  • Utilizing oncogenic Ras (Ha-ras, Ki-ras) and normal Ras activation models.
  • Employing Ras and mitogen-activated protein kinase kinase inhibitors.
  • Developing an alkaline phosphatase-tagged Mob-5 ligand to identify its receptor.

Main Results:

  • Identified and characterized mob-5, a novel oncogenic Ras target gene.
  • Mob-5 encodes a 23-kDa cytokine-like secreted protein.
  • Mob-5 expression is induced by oncogenic Ha-ras and Ki-ras, but not normal Ras.
  • Ras and MAPK pathway inhibitors abolished mob-5 expression and reversed transformation phenotype.
  • A putative Mob-5 receptor was identified on the cell surface of oncogenic Ras-transformed cells.

Conclusions:

  • Mob-5 is a novel oncogenic Ras target gene.
  • The Mob-5/Mob-5 receptor axis may constitute a new autocrine loop activated by Ras oncogenes.
  • This pathway could be a potential therapeutic target in Ras-driven cancers.

More Related Videos

Characterize Disease-related Mutants of RAF Family Kinases by Using a Set of Practical and Feasible Methods07:49

Characterize Disease-related Mutants of RAF Family Kinases by Using a Set of Practical and Feasible Methods

Published on: July 17, 2019

Related Concept Videos

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...
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:
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...
Receptor Tyrosine Kinases01:26

Receptor Tyrosine Kinases

Receptor tyrosine kinases or RTKs are membrane-bound receptors that phosphorylate specific tyrosine on protein substrates. RTKs regulate cellular growth, differentiation, survival, and migration. They contain an extracellular ligand binding domain, a transmembrane domain, and a cytosolic tail with intrinsic kinase activity. Several extracellular signaling molecules activate RTKs in one or more ways and relay the signal downstream. Ligands such as platelet-derived growth factor (PDGF) or...
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...
Abnormal Proliferation02:23

Abnormal Proliferation

Under normal conditions, most adult cells remain in a non-proliferative state unless stimulated by internal or external factors to replace lost cells. Abnormal cell proliferation is a condition in which the cell's growth exceeds and is uncoordinated with normal cells. In such situations, cell division persists in the same excessive manner even after cessation of the stimuli, leading to persistent tumors. The tumor arises from the damaged cells that replicate to pass the damage to the daughter...