Related Experiment Video

Updated: Aug 24, 2026

Screening and Identification of Small Peptides Targeting Fibroblast Growth Factor Receptor2 using a Phage Display Peptide Library
07:32

Screening and Identification of Small Peptides Targeting Fibroblast Growth Factor Receptor2 using a Phage Display Peptide Library

Published on: September 30, 2019

Downstream-of-FGFR is a fibroblast growth factor-specific scaffolding protein and recruits Corkscrew upon receptor

Valérie Petit1, Ute Nussbaumer, Caroline Dossenbach

  • 1Abteilung Zellbiologie, Biozentrum der Universität Basel, CH-4056 Basel, Switzerland.

Molecular and Cellular Biology
|April 15, 2004
PubMed

Insights

Downstream-of-FGFR (Dof) protein is crucial for Fibroblast Growth Factor Receptor (FGFR) signaling in Drosophila cell migration. Phosphorylation of Dof recruits Corkscrew (Csw), an essential step for Ras/MAPK pathway activation and cell movement.

Area of Science:

  • Cell Biology
  • Developmental Biology
  • Molecular Genetics

Background:

  • Fibroblast Growth Factor Receptor (FGFR) signaling regulates cell migration in various cell types.
  • The molecular mechanisms connecting FGFR activation to cytoskeletal changes during cell migration remain incompletely understood.

Purpose of the Study:

  • To functionally characterize Downstream-of-FGFR (Dof), a putative adapter protein in FGFR signaling.
  • To elucidate the role of Dof in linking FGFR activation to cytoskeletal rearrangements and cell migration in Drosophila.

Main Methods:

  • Reverse genetics, cell culture, and biochemical approaches were employed.
  • Functional characterization of Dof and its interaction with FGFRs and downstream components.
  • Identification of critical regions within Dof required for its function.

Main Results:

  • Dof acts as a specific substrate for Drosophila FGFRs.
  • Phosphorylation of tyrosine residue 515 in Dof is essential for recruiting the phosphatase Corkscrew (Csw).
  • Csw recruitment is vital for FGF-induced cell migration and Ras/MAPK pathway activation, though additional factors are necessary.

Conclusions:

  • Dof is a key mediator in FGFR-driven cell migration by facilitating Csw recruitment.
  • Ras/MAPK pathway activation alone is insufficient for complete cell migration; additional protein interactions are critical.
  • Further investigation into Dof-interacting proteins is needed to understand chemotactic responses.

More Related Videos

A High-throughput Cell Microarray Platform for Correlative Analysis of Cell Differentiation and Traction Forces12:04

A High-throughput Cell Microarray Platform for Correlative Analysis of Cell Differentiation and Traction Forces

Published on: March 1, 2017

A Cell-based Assay to Investigate Non-muscle Myosin II Contractility via the Folded-gastrulation Signaling Pathway in Drosophila S2R+ Cells07:15

A Cell-based Assay to Investigate Non-muscle Myosin II Contractility via the Folded-gastrulation Signaling Pathway in Drosophila S2R+ Cells

Published on: August 19, 2018

Related Concept Videos

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,...
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...
TGF - β Signaling Pathway01:16

TGF - β Signaling Pathway

The TGF-β signaling pathway regulates cell growth, differentiation, adhesion, motility, and development. TGF-β ligands that induce TGF-β signaling are synthesized in their latent form. Several proteases or cell surface receptors such as integrins act upon the latent form, releasing the active ligand. There are three types of mammalian TGF-βs: (TGF-β1, TGF-β2, and TGF-β3) that bind as homodimers or heterodimers to TGF-β receptors. The TGF-β receptors are of three kinds RI, RII, and RIII. The RI...
Fibronectins Connect Cells with ECM01:25

Fibronectins Connect Cells with ECM

Fibronectin is an adhesive glycoprotein present in the extracellular matrix of embryogenic and adult tissue. These molecules primarily aid in regulating cell motility and attachment. A fibronectin molecule is composed of two identical polypeptide chains attached to each other by a pair of disulfide bonds at the C-terminal.
Both proteoglycans and collagen are attached to fibronectin proteins, which, in turn, are attached to integrin proteins. These integrin proteins interact with transmembrane...
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...
Amplifying Signals via Enzymatic Cascade01:22

Amplifying Signals via Enzymatic Cascade

When a ligand binds to a cell-surface receptor, the receptor's intracellular domain changes shape, which may either activate its enzyme function or allow its binding to other molecules. The initial signal is amplified by most signal transduction pathways. This means that a single ligand molecule can activate multiple molecules of a downstream target. Proteins that relay a signal are most commonly phosphorylated at one or more sites, activating or inactivating the protein. Kinases catalyze the...