BSC 300 Fall 2024_Lecture #17_Oct24_Cell Signaling, Part 1 2

Lecture Overview

• Lecture #17: Signal Transduction and Cell Signaling, Part 1

• Major Topics Covered

  • 15.1 Signal Transduction Pathways: From Extracellular Signal to Cellular Response

  • 15.2 Studying Cell-Surface Receptors and Signal Transduction Proteins

  • 15.3 Structure and Mechanism of G Protein-Coupled Receptors

  • 15.4 Regulating Metabolism of Many Cells: G Protein-Coupled Receptors That Activate or Inhibit Adenylyl Cyclase

Learning Objectives

• Cell Signaling Principles

  • General principles of cell signaling

  • Types of signaling molecules

  • Generic signaling pathways

  • Signaling through trimeric G proteins linked to cell surface receptors

  • Differences between monomeric and trimeric G proteins

  • G protein accessory proteins and different secondary messengers

  • Activation and termination of signaling pathways

Signal Transduction Basics

• Extracellular Signal Response

  • All cells respond to extracellular signals activating plasma membrane or cytosolic receptors

  • Receptors act as transcription factors or activate G protein switches, regulating various pathways, generating second messengers

  • Kinases and phosphatases regulate protein activity to amplify intracellular signaling

Overview of Cell Signaling

• Extracellular Signaling Molecules

  • Also called ligands or first messengers

  • Synthesized and secreted by specialized signaling cells

  • External molecules can also act as ligands (e.g., toxins activating cell stress response)

• Signal Response

  • Target cells express specific receptor proteins that bind to signals

Molecular Roles in Signal Transduction

• Signal Processing

  • Converts impulses or stimuli chemically or physically through cell responses to signals

  • Activated receptors relay information to cytoplasmic proteins, amplifying, integrating, and executing cellular responses

Types of Signaling Molecules

• Hydrophobic Signaling Molecules

  • Diffuse through membranes, bind to cytosolic receptors, affect gene expression

• Hydrophilic Signaling Molecules

  • Require transmembrane receptors, cannot diffuse across membranes

  • Trigger conformational changes and relay signals via second messengers

Mechanisms of Signal Transduction

• Activation Steps

  • Signal binds to receptor leading to conformational change

  • Activated receptors stimulate downstream proteins and small molecules

  • Effectors modify target proteins for short or long-term responses

• Cellular Response

  • Short-term changes: metabolism, movement

  • Long-term changes: gene expression

Termination of Signaling

• Down-modulation of Cellular Response

  • Involves negative feedback mechanisms and destruction of extracellular signals

  • Enzymatic pathways can also regulate signaling positively or negatively

  • Mechanisms include GTP hydrolysis, breakdown of second messengers, or receptor degradation

Types of Extracellular Signaling

• Endocrine Signaling

  • Hormones like epinephrine and insulin travel through circulatory systems affecting distant target cells

• Paracrine Signaling

  • Affects nearby cells, involves neurotransmitters and growth factors

• Neuronal Signaling

  • Long-distance signaling via electrical impulses and neurotransmitters

• Autocrine Signaling

  • Cells respond to self-secreted signals

• Juxtacrine Signaling

  • Involves direct contact between neighboring cells or signaling through gap junctions

Fundamental Elements of Cell Signaling Systems

• Receptor Design

  • Receptors receive messages, generating second messengers and recruiting proteins that regulate signaling pathways

G Protein-Coupled Receptors (GPCRs)

• Overview

  • Largest superfamily of proteins responding to various signals

  • Seven membrane-spanning domains interacting with cytoplasmic G proteins

  • Ligands include hormones, neurotransmitters, and more

• Mechanism of Activation

  • Ligand binding alters receptor conformation, activating G proteins

  • Active G proteins stimulate second messenger production for cellular responses

Secondary Messengers

• Common Types

  • cAMP: activates PKA

  • cGMP: activates PKG

  • IP3/DAG: regulate calcium release and PKC activation

  • Calcium ions: activates various proteins like calmodulin

  • Nitric Oxide: important for autocrine signaling

Drug Interactions and Receptor Function

• Receptor Binding

  • Synthetic analogs (agonist and antagonist) can modulate physiological responses

  • Epo hormone activation of signaling pathways via phosphorylation observed using Western blotting

Key Takeaways on GPCRs and Adenylyl Cyclase

• Regulatory Functions

  • GPCRs affect cellular activities by regulating cAMP levels through adenylyl cyclase

  • cAMP impacts multiple cellular activities including metabolism and gene expression

• Glycogen Metabolism

  • Hormonal regulation governs cyclic processes between synthesis and breakdown in liver and muscle cells

Signal Amplification

• Amplification Mechanism

  • Initial signals produce widespread effects through cascades, activating multiple G proteins and amplifying the effects of signaling pathways

Conclusion & Further Studies

• Next Lecture: Explore additional signal transduction details and further chapters.

• Reading Assignments: Chapter 15: pages 690-704, Chapter 16: pages 705-726.