Related Experiment Video

Updated: Sep 20, 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

Ras is a mediator of TGFbeta1 signaling in developing chick ciliary ganglion neurons

Loic Lhuillier1, Stuart E Dryer

  • 1Department of Biology and Biochemistry, University of Houston, Houston, TX 77204-5513, USA.

Brain Research
|August 14, 2003
PubMed

Insights

Transforming growth factor beta1 (TGFβ1) regulates large-conductance Ca(2+)-activated K(+) channels (K(Ca)) in developing neurons. Ras signaling pathways mediate this TGFβ1 effect, impacting neuronal development.

Area of Science:

  • Neuroscience
  • Molecular Biology
  • Cell Signaling

Background:

  • Large-conductance Ca(2+)-activated K(+) channels (K(Ca)) are crucial for neuronal function.
  • Target-derived TGFβ1 is known to regulate K(Ca) channel expression in chick ciliary ganglion neurons.

Purpose of the Study:

  • To investigate the role of Ras signaling in TGFβ1-mediated regulation of K(Ca) channels.
  • To elucidate the molecular mechanisms by which TGFβ1 influences neuronal development via K(Ca) channels.

Main Methods:

  • Utilized Ras protein farnesyl transferase inhibitors (manumycin-A and FTI-277) to block Ras activity.
  • Employed overexpression of dominant-negative Ras (RasN17) in ciliary neurons.
  • Assessed TGFβ1-evoked increases in K(Ca) expression and SMAD2 phosphorylation.

Main Results:

  • TGFβ1-induced K(Ca) expression was significantly inhibited by Ras farnesyl transferase inhibitors.
  • Overexpression of RasN17 also blocked TGFβ1's effect on K(Ca) expression.
  • Manumycin-A treatment reduced TGFβ1-induced SMAD2 phosphorylation, indicating feedback onto SMAD signaling.

Conclusions:

  • Ras signaling pathways are essential mediators of TGFβ1's pleiotropic effects in developing neurons.
  • Ras acts upstream of or in parallel with SMAD signaling in response to TGFβ1.
  • This study reveals a novel crosstalk between Ras and TGFβ1/SMAD signaling in neuronal development.

More Related Videos

Application of Impermeable Barriers Combined with Candidate Factor Soaked Beads to Study Inductive Signals in the Chick08:04

Application of Impermeable Barriers Combined with Candidate Factor Soaked Beads to Study Inductive Signals in the Chick

Published on: November 17, 2016

Microinjection of Recombinant RCAS(A) Retrovirus into Embryonic Chicken Lens04:58

Microinjection of Recombinant RCAS(A) Retrovirus into Embryonic Chicken Lens

Published on: September 1, 2023

Related Concept Videos

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:
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...
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...
Activation and Inactivation of G Proteins01:22

Activation and Inactivation of G Proteins

Heterotrimeric G proteins are guanine nucleotide-binding proteins. As the name suggests, heterotrimeric G proteins are composed of three subunits: alpha, beta, and gamma. They remain GDP-bound or GTP-bound inside the cells and switch between inactive/active states. The Gα subunit possesses the nucleotide-binding pocket that binds guanine nucleotides and switches between GDP or GTP-bound states. In contrast, the Gꞵ and Gγ subunits are always bound together with high affinity and are together...
Determination01:51

Determination

During embryogenesis, cells become progressively committed to different fates through a two-step process: specification followed by determination. Specification is demonstrated by removing a segment of an early embryo, “neutrally” culturing the tissue in vitro—for example, in a petri dish with simple medium—and then observing the derivatives. If the cultured region gives rise to cell types that it would normally generate in the embryo, this means that it is specified. In contrast, determination...
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...