FFP1 - Enzyme-linked and intracellular receptors (1)

FFP1 – Enzyme-linked and Intracellular Receptors

Dr. Roger PrestonSchool of Pharmacy & Biomolecular SciencesRCSI Royal College of Surgeons in Ireland

Learning Outcomes

  • Explain the structure and function of:

    • Tyrosine kinase-linked receptors

    • Ligand-gated ion channels

    • Intracellular receptors

  • Outline the signaling cascade for each of these receptors.

Receptor-Response Theory

  • Concept Overview

    • Reception: Initial binding of the signal molecule to the receptor.

    • Transduction: Conversion of the signal into cellular responses.

    • Response: Outcomes of the signal-transduction pathway.

Types of Receptors

  1. Ligand-gated ion channels

  2. G-protein coupled receptors

  3. Tyrosine-kinase receptors

  4. Intracellular receptors

  • Agonist Activation

    • Activation involves:

      • Na+ influx through ion channels

      • G-Protein interactions

      • Phosphorylation of tyrosines

      • Generation of second messengers

      • Transcriptional activation.

Receptor Tyrosine Kinases (RTK)

  • Structure and Function

    • Extracellular Domain: Binds the signal (ligand).

    • Intracellular Tyrosine Kinase Domain: Transmits the signal upon ligand binding.

  • Mechanism of Action

    1. Ligand Binding: Leads to dimerization and autophosphorylation.

    2. Adapter Protein Binding: Grb2 connects signalling molecules (SH2 and SH3 domains).

    3. Ras Activation: GTPase Ras activates cell signalling following GDP removal by SoS.

    4. Cell Signalling Outcomes: Changes in protein activity and gene expression, leading to cell proliferation.

Ligand-Gated Ion Channels

  • Structure and Function

    • Composed of receptor subunits forming a central pore.

    • Transmembrane receptor directly coupled to ion channels (e.g., neurotransmitters).

  • Mechanism of Action

    • Hormone Binding: Binding opens the channel, allowing ion influx.

    • Stages of Activity:

      1. Resting: Able to respond to ligand stimulus.

      2. Activated: Open for ion flux.

      3. Inactivated: Desensitized to stimulus.

Nuclear Receptors

  • Structure and Function

    • Example: Glucocorticoid receptor.

    • Contains:

      • Hormone binding site.

      • DNA binding site to interact with the genome.

  • Mechanism of Action

    1. Intracellular Binding: Steroid hormone interacts with the receptor, detaching the chaperone.

    2. Translocation: The steroid-receptor complex moves to the nucleus.

    3. DNA Binding: Binds to specific genomic regions to initiate gene expressions.

    4. Gene Expression Change: Triggers transcriptional programs leading to an anti-inflammatory response.

Summary of Key Receptors and Mechanisms

  • Ligand-gated ion channels, G-protein coupled receptors, Tyrosine-kinase receptors, and Intracellular receptors all participate in diverse signaling pathways and outcomes in cellular functions.

What We Have Learned

  • Understanding receptor signaling concepts and the structure/function of various receptors enhances knowledge of cellular communication and response to stimuli.

Further Reading and Viewing