BIOL230W, Week 7 Signaling Pathways

BIOL230W - Week 7 Notes

Day 1 Learning Objectives

• General Process of Signaling: Understand signals, receptors, second messengers, and final targets/effectors.
• Protein Conformation Changes: Define and understand the impact on function.
• Comparison of Receptor Types: GPCRs, RTKs, intracellular androgen receptors.
• GPCR Characteristics: Seven transmembrane regions; ligand and G-protein binding.
• Domains vs. Structural Motifs: Differences and significance.
• Using Legends in Information Integration: Understand how legends can aid in comprehension of protein function.

Key Words

• Signal (ligand)
• Receptor
• Conformation change
• GPCR (G-protein, heterotrimer, GAP, GEF)
• Peptide motif

Signaling Pathways Overview

• Communication in Cells: Cells must communicate with each other and their environment.
  • How does an extracellular signal induce intracellular changes?
  • What molecules are involved?
  • What physiological changes occur?
  • Impact of blocked or altered pathways?

Fundamentals of Signaling

• Signal: A chemical signal, often termed a ligand.
• Receptor: Often a protein that senses signals, causing a conformation change.
• Transduction: The process of signal relay through effector proteins, often using secondary messengers.
  • Final Effector: Last protein altered by the pathway, leading to physiological or gene expression changes.

Signals

• Types of Signals: Include proteins, hormones, growth factors, and environmental signals (e.g., gravity, heat).

Receptors

• Characterization: Integral proteins that sense signals through ligand binding, leading to conformation changes (e.g., GPCRs, Tyrosine Kinases).

Receptors and G-Protein Coupled Pathways

• GPCRs: Integral membrane proteins with extracellular ligand-binding domains and intracellular G-protein coupling domains.
• G-Proteins: Heterotrimeric proteins (Ga, Gb, Gg) activated by ligand-receptor binding.
  • Conformational changes trigger further signaling cascades.

Types of Receptors: RTKs

• Receptor Tyrosine Kinases (RTKs):
  • Binding of ligand causes dimerization and activation of the tyrosine kinase domain, which phosphorylates tyrosines (autophosphorylation).

Second Messengers

• Role: Transduce signals following primary messenger action.
• Examples: cAMP, DAG, IP3, Ca2+.
  • cAMP is produced via adenylyl cyclase activation, while IP3 and DAG arise from PIP2 cleavage.

Effector Molecules

• Kinases vs. Phosphatases:
  • Kinase: Adds phosphate groups, generally activating proteins.
  • Phosphatase: Removes phosphate groups, typically inactivating proteins.

Day 2 Learning Objectives

• Continued Study of Signaling: Focus on specific mechanisms, including receptor activation and second messenger synthesis.
• Upstream vs. Downstream Events: Understanding the positioning within a signaling pathway and how they relate to overall function.

Final Effectors

• Consequence of Pathway Activation:
  • Can alter gene expression (via transcription factors).
  • Directly influences cell growth/metabolism, e.g., glucose transport.

Pathways Exploration

• Inflammation Pathway: Questions focused on the effects of ligand and enzyme inhibition on pathway activity.
• Hippo Pathway: Questions on tissue growth regulation and specific functionality under genetic influences.

Summary for Exam Preparation

• Understand the definitions and interrelatedness of signals, receptors, transduction processes, and effectors.
• Be able to identify and explain different pathway components and how manipulation at various points affects cellular outcomes.