Related Experiment Video

Updated: Jul 10, 2026

Light-mediated Reversible Modulation of the Mitogen-activated Protein Kinase Pathway during Cell Differentiation and Xenopus Embryonic Development
09:32

Light-mediated Reversible Modulation of the Mitogen-activated Protein Kinase Pathway during Cell Differentiation and Xenopus Embryonic Development

Published on: June 15, 2017

Src kinase modulates the activation, transport and signalling dynamics of fibroblast growth factor receptors

Emma Sandilands1, Shiva Akbarzadeh, Anna Vecchione

  • 1Cancer Research UK Beatson Institute for Cancer Research, Garscube Estate, Switchback Road, Glasgow G61 1BD, UK.

EMBO Reports
|November 3, 2007
PubMed

Insights

The non-receptor tyrosine kinase Src regulates fibroblast growth factor receptor 1 (FGFR1) signaling dynamics. Src kinase activity and localization are crucial for FGFR1 internalization and downstream pathway activation.

Area of Science:

  • Cellular signaling and kinase regulation
  • Receptor tyrosine kinase pathways

Background:

  • Non-receptor tyrosine kinase Src is recruited to activated fibroblast growth factor receptor (FGFR) complexes via the adaptor protein FRS2.
  • FGFR signaling plays critical roles in various cellular processes, including proliferation, differentiation, and survival.

Purpose of the Study:

  • To investigate the role of Src kinase activity in regulating the dynamics of FGFR1 signaling.
  • To elucidate the mechanisms by which Src influences FGFR1 localization, internalization, and downstream signaling.

Main Methods:

  • Co-localization studies to assess the spatial relationship between activated Src and FGFR1.
  • Chemical and genetic inhibition of Src family kinases and FGFR1.
  • Analysis of downstream signaling pathways, including phosphoinositide-3 kinase-Akt and extracellular signal-regulated kinase.

Main Results:

  • Activated Src co-localizes with activated FGFR1 at the plasma membrane, requiring kinase activity from both.
  • Src-mediated FGFR1 internalization depends on RhoB endosomes and an intact actin cytoskeleton.
  • Src inhibition differentially affects FGFR1 downstream signaling: phosphoinositide-3 kinase-Akt activation is attenuated, while extracellular signal-regulated kinase activation is delayed and fails to attenuate.

Conclusions:

  • Src kinase activity is essential for the spatiotemporal regulation of FGFR1 signaling.
  • Src influences FGFR1 trafficking and activation of distinct downstream pathways, highlighting pathway-specific regulation.
  • Understanding Src's role in FGFR1 signaling provides insights into receptor dynamics and downstream effectors.

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

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

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...
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...
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...
Interactions Between Signaling Pathways01:19

Interactions Between Signaling Pathways

Signaling cascades usually lack linearity. Multiple pathways interact and regulate one another, allowing cells to integrate and respond to diverse environmental stimuli.
Convergence and divergence, and cross-talk between signaling pathways
Two distinct signaling pathways can converge on a single functional unit, which may either be a single protein or a complex of proteins. The response is either functionally distinct or synergistic between the two pathways but different from the response...
PI3K/mTOR/AKT Signaling Pathway01:22

PI3K/mTOR/AKT Signaling Pathway

The mammalian target of rapamycin  (mTOR) is a serine/threonine kinase that regulates growth, proliferation, and cell survival in response to hormones, growth factors, or nutrient availability. This kinase exists in two structurally and functionally distinct forms: mTOR complex 1  (mTORC1) and mTOR complex 2  (mTORC2). The first form (mTORC1) is composed of a rapamycin-sensitive Raptor and proline-rich Akt substrate, PRAS40. In contrast,  mTORC2 consists of a rapamycin-insensitive companion...