BIOL230W Week 7 Detailed Notes

BIOL230W Week 7 Day 1-3 Notes

Day 1 Learning Objectives

• Signaling Process Overview: Understand how signaling occurs, including key components such as signals, receptors, second messengers, and effector proteins.
• Protein Conformation Changes: Define how changes in the conformation of proteins lead to variations in their functions, impacting signaling pathways.
• Receptor Comparison: Compare and contrast characteristics of G-protein coupled receptors (GPCRs), Receptor Tyrosine Kinases (RTKs), and intracellular androgen receptors.
• GPCR Characteristics: Identify the major features of GPCRs, such as the seven transmembrane regions, ligand binding sites, and G-protein interaction regions.
• Domains and Motifs: Explain differences between domains, structural motifs, and peptide motifs in the context of proteins.
• Use of Legends: Apply legends to integrate and interpret information regarding protein functions.

Key Terms

• Signal (ligand): A chemical that elicits a cellular response.
• Receptor: Proteins that detect signals and initiate transmission of the signal.
• Conformation Change: Structural modification in proteins that alters function.
• GPCR: G-protein Coupled Receptor; integral membrane protein involved in signal transduction.
• Peptide Motif: Specific sequences in proteins critical for their function.

Fundamentals of Signaling

• Signal: Can arise from environmental or cellular sources, including proteins, hormones, and growth factors.
• Receptor Function: Integral proteins that sense and respond to signals, causing conformational changes upon binding.
• Signal Transduction: The process of relaying a signal through a cell involves the alteration of effector proteins, often mediated by secondary messengers.
• Final Effector: The last modulated protein in the pathway, often leading to changes in physiological responses or gene expression.

Parts of a Signaling Pathway

1. Signals: Various ligands from environmental or cellular origins.
2. Receptors: Proteins that detect and bind signals, leading to their activation.
3. Transduction: The process of transmitting signals inside the cell, often involving secondary messengers.
4. Effectors: Proteins that execute downstream effects, resulting in a cellular response.
5. Physiological Changes: Changes that occur at the cellular level, potentially impacting gene expression and cellular behavior.

Types of Receptors

G-Protein Coupled Receptors (GPCRs)

• Structure: Integral membrane proteins with extracellular ligand-binding domains and intracellular G-protein interaction domains.
• G-Proteins: Composed of three subunits and play a key role in signal transduction upon receptor activation (conformation change from ligand binding).

Receptor Tyrosine Kinases (RTKs)

• Activate through ligand binding, leading to dimerization and autophosphorylation of tyrosines, enabling signal transduction through downstream effectors.

Conformational Changes in Receptors

• Ligand binding induces specific changes in receptor conformation, which is essential for the transmission of the signaling cascade.

Second Messengers

• cAMP (Cyclic Adenosine Monophosphate): Commonly associated with GPCRs, synthesized from ATP through adenylyl cyclase.
• DAG (Diacylglycerol) and IP3 (Inositol trisphosphate): Derived from membrane phospholipids, involved in further signaling cascades, specifically in calcium release.
• Calcium Ions (Ca²⁺): Act as secondary messengers that can modulate various cellular activities.

Amplifying the Signal: Effectors

• Kinases: Enzymes that add phosphate groups to proteins, often activating or inactivating them.
• Phosphatases: Remove phosphate groups, counteracting the actions of kinases and helping to regulate signaling pathways.

Final Effector Protein

• The last modified protein in a signaling pathway, can lead to gene expression changes or physiological responses (e.g., metabolism regulation).

Upstream vs. Downstream Events

• Upstream Events: Early steps in the signaling process.
• Downstream Events: Later responses that occur following the initial signal detection and transduction.

Pathway Examples and Implications

• Inflammation Pathway: Investigate the effects of blocking certain enzymes or proteins in a pathway.
• Hippo Pathway: Understanding growth regulation at a genetic level through signaling inhibition or enhancement.