Related Experiment Video

Updated: Aug 6, 2026

Methods to Study Mrp4-containing Macromolecular Complexes in the Regulation of Fibroblast Migration
10:43

Methods to Study Mrp4-containing Macromolecular Complexes in the Regulation of Fibroblast Migration

Published on: May 19, 2016

Fibroblast growth factor-2 induces the activation of Src through Fes, which regulates focal adhesion disassembly

Shigeru Kanda1, Yasuyoshi Miyata, Hiroshi Kanetake

  • 1Department of Molecular Microbiology and Immunology, Division of Endothelial Cell Biology, Nagasaki University Graduate School of Biomedical Science, Japan. skanda-jua@umin.net

Experimental Cell Research
|August 4, 2006
PubMed

Insights

Fibroblast growth factor-2 (FGF-2) triggers cell movement by promoting focal adhesion (FA) disassembly. This study reveals that Fes activation by FGF-2 enhances focal adhesion kinase (FAK)-dependent Src activation within FAs, driving cell migration.

Area of Science:

  • Cell Biology
  • Molecular Biology
  • Biochemistry

Background:

  • Cell migration is crucial for biological processes and relies on focal adhesion (FA) dynamics.
  • Fibroblast growth factor-2 (FGF-2) is known to induce FA disassembly and direct cell chemotaxis in endothelial cells.
  • Previous work implicated Src and Fes tyrosine kinases in FGF-2-mediated cell migration.

Purpose of the Study:

  • To investigate the interplay between Src and Fes kinases in FGF-2-induced focal adhesion disassembly.
  • To elucidate the signaling pathway by which FGF-2 regulates focal adhesion turnover and cell migration.

Main Methods:

  • Utilized the murine brain capillary endothelial cell line (IBE) and a dominant-negative Fes mutant (KE5-15 cells).
  • Employed small interfering RNA (siRNA) to downregulate Fes and focal adhesion kinase (FAK).
  • Analyzed protein activation, binding, and phosphorylation (Src, Fes, Cas, FAK) following FGF-2 treatment using Western blotting and immunofluorescence.

Main Results:

  • FGF-2-induced FA disassembly was abrogated in KE5-15 cells, indicating Fes dependence.
  • FGF-2 treatment activated Src and promoted its binding to and phosphorylation of Cas in wild-type IBE cells, but not in KE5-15 cells.
  • FAK activation and Src-mediated tyrosine phosphorylation were delayed in KE5-15 cells.
  • FGF-2-induced Src activation within FAs was dependent on Fes and FAK, as shown by siRNA-mediated downregulation.

Conclusions:

  • FGF-2 activates Fes, which in turn enhances FAK-dependent Src activation within focal adhesions.
  • This cascade promotes the disassembly of focal adhesions, facilitating FGF-2-directed cell migration.
  • The findings reveal a novel signaling mechanism regulating cell motility through kinase crosstalk within focal adhesions.

More Related Videos

An Immunofluorescent Method for Characterization of Barrett’s Esophagus Cells08:54

An Immunofluorescent Method for Characterization of Barrett’s Esophagus Cells

Published on: July 20, 2014

Examining the Dynamics of Cellular Adhesion and Spreading of Epithelial Cells on Fibronectin During Oxidative Stress10:57

Examining the Dynamics of Cellular Adhesion and Spreading of Epithelial Cells on Fibronectin During Oxidative Stress

Published on: October 13, 2019

Related Concept Videos

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...
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...
Cell-matrix's Response to Mechanical Forces01:13

Cell-matrix's Response to Mechanical Forces

In animal cells, the extracellular matrix allows cells within tissues to withstand external stresses and transmits signals from the outside of the cell to the inside. The extracellular matrix is extensive, and its composition varies between different types of tissues. For example, the reticular fibers and ground substance make up the ECM in loose connective tissue, while collagen and bone minerals make up the ECM of bone tissue. 
Anchoring junctions mechanically attach a cell to the...
Mechanism of Filopodia Formation01:39

Mechanism of Filopodia Formation

Filopodia are thin, actin-rich cellular protrusions that play an important role in many fundamental cellular functions. They vary in their occurrence, length, and positioning in different cell types, suggesting their diverse roles.
Their main function is to guide migrating cells during normal tissue morphogenesis or cancer metastasis by recognizing and making initial contacts with the extracellular matrix. However, they can also act as stationary cell anchors or help to establish communication...
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...
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...