Related Experiment Video

Updated: May 8, 2026

Spatio-Temporal Manipulation of Small GTPase Activity at Subcellular Level and on Timescale of Seconds in Living Cells
10:27

Spatio-Temporal Manipulation of Small GTPase Activity at Subcellular Level and on Timescale of Seconds in Living Cells

Published on: March 9, 2012

A lipid-anchored Grb2-binding protein that links FGF-receptor activation to the Ras/MAPK signaling pathway

H Kouhara1, Y R Hadari, T Spivak-Kroizman

  • 1Department of Pharmacology, New York University Medical Center, New York 10016, USA.

Cell
|May 30, 1997
PubMed

Insights

A novel protein, FRS2, links growth factor receptors to MAPK signaling. Myristylation is crucial for its membrane localization and activation of cell growth pathways, identifying it as a key signaling intermediate.

Area of Science:

  • Cellular signaling
  • Molecular biology
  • Signal transduction

Background:

  • The Ras/MAPK pathway is vital for cell proliferation and differentiation.
  • Growth factors like FGF and NGF activate this pathway.

Purpose of the Study:

  • To identify and characterize novel proteins involved in FGF and NGF signaling.
  • To elucidate the role of FRS2 in linking receptor activation to downstream signaling.

Main Methods:

  • Protein purification and cloning of FRS2.
  • Analysis of protein modification (myristylation) and localization.
  • Assays for tyrosine phosphorylation, Grb2/Sos binding, and MAPK activation.

Main Results:

  • FRS2 is a novel, myristylated protein.
  • Myristylation is essential for FRS2 membrane localization, phosphorylation, and Grb2/Sos recruitment.
  • FRS2 links FGF receptor activation to MAPK pathway activation.

Conclusions:

  • FRS2 acts as a lipid-anchored docking protein essential for FGF-induced MAPK signaling.
  • FRS2 is likely identical to SNT, a known target of FGF and NGF receptors.

More Related Videos

A High-content Imaging Workflow to Study Grb2 Signaling Complexes by Expression Cloning10:52

A High-content Imaging Workflow to Study Grb2 Signaling Complexes by Expression Cloning

Published on: October 30, 2012

Bioluminescence Resonance Energy Transfer (BRET)-Based Assay for Measuring Interactions of CRAF with 14-3-3 Proteins in Live Cells06:44

Bioluminescence Resonance Energy Transfer (BRET)-Based Assay for Measuring Interactions of CRAF with 14-3-3 Proteins in Live Cells

Published on: March 1, 2024

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...
Assembly of Signaling Complexes01:30

Assembly of Signaling Complexes

Multiprotein signaling complexes are formed in a dynamic process involving protein-protein interactions at the cytoplasmic domain of transmembrane receptors or enzymatic and non-enzymatic proteins associated with the receptor. These complexes ensure the activation and propagation of intracellular signals that regulate cell functions.
Interaction domains in cell signaling
Interaction domains recognize exposed features of their binding partners containing post-translationally modified sequences,...
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...
IP3/DAG Signaling Pathway01:11

IP3/DAG Signaling Pathway

Membrane lipids such as phosphatidylinositol (PI) are precursors for several membrane-bound and soluble second messengers. Specific kinases phosphorylate PI and produce phosphorylated inositol phospholipids. One such inositol phospholipids are the  phosphatidylinositol-4,5 bisphosphate [PI(4,5)P2], present in the inner half of the lipid bilayer. Upon ligand binding, GPCR stimulates Gq proteins to turn on phospholipase Cꞵ. Activated phospholipase Cꞵ cleaves PI(4,5)P2 and produces two-second...
Intracellular Signaling Affects Focal Adhesions01:17

Intracellular Signaling Affects Focal Adhesions

Integrins act both as extracellular input receivers and as intracellular processing activators. As their name suggests, integrins are entirely integrated into the membrane structure. Their hydrophobic membrane-spanning regions interact with the phospholipid bilayer's hydrophobic region. These membrane receptors provide extracellular attachment sites for effectors like hormones and growth factors. They activate intracellular response cascades when their effectors are bound and active.
Some...