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Related Concept Videos

Transducer Mechanism: G Protein–Coupled Receptors01:30

Transducer Mechanism: G Protein–Coupled Receptors

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G Protein–Coupled Receptors (GPCRs) are membrane-bound receptors that transiently associate with heterotrimeric G proteins and induce an appropriate response to various stimuli. GPCRs regulate critical physiological pathways and are excellent drug targets for treating diseases such as diabetes, cancer, obesity, depression, or Alzheimer's. Nearly 35% of approved drugs implement their therapeutic effects by selectively interacting with specific GPCRs.
GPCRs are also called heptahelical,...
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G Protein-coupled Receptors01:15

G Protein-coupled Receptors

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G Protein-Coupled Receptors or GPCRs are membrane-bound receptors that transiently associate with heterotrimeric G proteins and induce an appropriate response to sensory stimuli such as light, odors, hormones, cytokines, or neurotransmitters.
GPCRs are also called heptahelical, 7TM, or serpentine receptors, and consist of seven (H1-H7) transmembrane alpha-helices that span the bilayer to form a cylindrical core. The transmembrane helices are connected by three extracellular loops and three...
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Activation and Inactivation of G Proteins01:22

Activation and Inactivation of G Proteins

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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...
12.0K
IP3/DAG Signaling Pathway01:11

IP3/DAG Signaling Pathway

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Membrane lipids such as phosphatidylinositol (PI) are precursors for several membrane-bound and soluble second messengers. Specific kinases phosphorylate PI and produce phosphorylated inositol phospholipids. One such inositol phospholipids are the  phosphatidylinositol-4,5 bisphosphate [PI(4,5)P2], present in the inner half of the lipid bilayer. Upon ligand binding, GPCR stimulates Gq proteins to turn on phospholipase Cꞵ. Activated phospholipase Cꞵ cleaves PI(4,5)P2 and...
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G-protein Coupled Receptors01:21

G-protein Coupled Receptors

133.2K
G-protein coupled receptors are ligand binding receptors that indirectly affect changes in the cell. The actual receptor is a single polypeptide that transverses the cell membrane seven times creating intracellular and extracellular loops. The extracellular loops create a ligand specific pocket which binds to neurotransmitters or hormones. The intracellular loops holds onto the G-protein.
133.2K
GPCRs Regulate Adenylyl Cylase Activity01:09

GPCRs Regulate Adenylyl Cylase Activity

7.9K
Some GPCRs transmit signals through adenylyl cyclase (AC), a transmembrane enzyme. AC helps synthesize second messenger cyclic adenosine monophosphate (cAMP). AC catalyzes cyclization reaction and converts ATP to cAMP by releasing a pyrophosphate. The pyrophosphate is further hydrolyzed to phosphate by the enzyme pyrophosphatase, which drives cAMP synthesis to completion. However, cAMP is rapidly degraded to 5′ AMP by the enzymes phosphodiesterase (PDE), preventing overstimulation of...
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Related Experiment Video

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Characterization of G Protein-coupled Receptors by a Fluorescence-based Calcium Mobilization Assay
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Characterization of G Protein-coupled Receptors by a Fluorescence-based Calcium Mobilization Assay

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PDGFs and their receptors.

Andrius Kazlauskas1

  • 1Schepens Eye Research Institute, Massachusetts Eye and Ear Institute, 20 Staniford St, Boston, MA 02114, United States.

Gene
|March 8, 2017
PubMed
Summary

Platelet-derived growth factor (PDGF) and its receptor (PDGFR) are vital for blood vessel formation. Understanding PDGFR activation mechanisms is key to developing targeted therapies for diseases involving deregulated growth factor signaling.

Area of Science:

  • Molecular Biology
  • Cell Biology
  • Biochemistry

Background:

  • The Platelet-Derived Growth Factor (PDGF)/PDGFR receptor (PDGFR) family plays a critical role in physiological processes, including pericyte migration and proliferation, essential for blood vessel development and function.
  • While ligand-dependent activation is the primary mechanism for PDGFR kinase activity, alternative activation pathways also exist.
  • Aberrant PDGFR signaling is implicated in various pathological conditions, highlighting its significance as a therapeutic target.

Purpose of the Study:

  • To elucidate the diverse activation mechanisms of the PDGF/PDGFR family.
  • To identify specific PDGFRs involved in pathological processes.
  • To explore the development of next-generation therapies targeting the PDGF/PDGFR pathway.

Main Methods:

Keywords:
Activation of receptor tyrosine kinasesIndirect activation of PDGFRNon-PDGFsPDGFPDGFR

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  • Review of existing literature on PDGF/PDGFR signaling pathways.
  • Analysis of studies investigating PDGFR activation modes.
  • Examination of research on PDGFR involvement in disease pathogenesis.

Main Results:

  • Confirmed that ligand-dependent de-repression is the major PDGFR activation mode.
  • Identified additional, less-understood mechanisms of PDGFR activation.
  • Highlighted the contribution of deregulated PDGFR activity to various pathologies.

Conclusions:

  • A deeper understanding of PDGFR activation mechanisms and specific receptor involvement in disease is crucial.
  • Development of biomarkers for PDGFR activation amplitude and mode is needed.
  • Receptor-specific antagonists are essential for advancing next-generation PDGF/PDGFR-targeted therapies.