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Related Concept Videos

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...
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...
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...
Non-Canonical Wnt Signaling Pathways01:41

Non-Canonical Wnt Signaling Pathways

Wnt is a zygotic effect gene that is expressed during very early embryonic development. It regulates various processes in animals starting from early development through the adult stage, such as organogenesis in the embryo and maintenance of neuronal and blood stem cells. Wnt proteins can induce a wide variety of intracellular pathways depending upon the specific abilities of different Wnt ligands to form a complex with shared and cognate receptors in the presence of different co-receptors. The...
Non-Canonical Wnt Signaling Pathways01:41

Non-Canonical Wnt Signaling Pathways

Wnt is a zygotic effect gene that is expressed during very early embryonic development. It regulates various processes in animals starting from early development through the adult stage, such as organogenesis in the embryo and maintenance of neuronal and blood stem cells. Wnt proteins can induce a wide variety of intracellular pathways depending upon the specific abilities of different Wnt ligands to form a complex with shared and cognate receptors in the presence of different co-receptors. The...
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,...

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Isolation of Whole Cell Protein Lysates from Mouse Facial Processes and Cultured Palatal Mesenchyme Cells for Phosphoprotein Analysis
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Multiple signaling pathways converge to regulate bone-morphogenetic-protein-dependent glial gene expression.

Justin J Dore1, John C DeWitt, Nithya Setty

  • 1Department of Biology and Volen National Center for Complex Systems, Brandeis University, Waltham, Mass. 02454, USA.

Developmental Neuroscience
|March 28, 2009
PubMed
Summary

Bone morphogenetic proteins (BMPs) influence glial cell development by activating Smad, PI3K, and MEK/ERK pathways. These pathways indirectly promote GFAP expression via Sp1, impacting peripheral nervous system formation.

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Area of Science:

  • Developmental neuroscience
  • Cell signaling
  • Glial cell biology

Background:

  • Bone morphogenetic proteins (BMPs) are crucial extracellular cues in neural development.
  • BMPs promote neuronal differentiation but inhibit mature Schwann cell phenotypes.
  • Understanding BMP signaling in glial differentiation is key to neural development.

Purpose of the Study:

  • Investigate BMP-activated intracellular pathways driving early glial gene expression.
  • Elucidate how signaling interactions influence cell fate in neural crest lineages.
  • Determine the mechanisms by which BMPs regulate GFAP expression.

Main Methods:

  • Utilized a neural-crest-derived cell line resembling immature Schwann cells.
  • Analyzed BMP2-induced signaling via Smad, PI3K, and MEK/ERK pathways.
  • Assessed GFAP promoter activity and the role of immediate early genes and Sp1.

Main Results:

  • BMP2 promotes GFAP expression through Smad, PI3K, and MEK/ERK signaling.
  • Smads appear to indirectly regulate GFAP, as consensus sites are absent.
  • BMP2 induces immediate early genes and Sp1, which contribute to GFAP promoter activity.

Conclusions:

  • Kinase pathways play significant roles in BMP-mediated glial differentiation.
  • Indirect Smad signaling via Sp1 is a novel mechanism in BMP-driven GFAP expression.
  • Differential signaling networks contribute to BMPs' diverse effects on neural development.