Lecture+_+4+Signal+Transduction+Lecture+notes-1 (1)

SIGNAL TRANSDUCTION LECTURE NOTES

Learning Objectives

• Cell-Cell Communication: Explain the importance in metabolic regulation.

• Types of Receptors: List and understand the four different types of receptors and their mechanisms.

• Examples of Receptors: Provide examples for each type of receptor.

• Second Messenger Systems: Describe adenylate cyclase and phosphoinositide systems.

• Components of Signaling Systems: Indicate receptors, G-proteins, and effector enzymes involved.

• Second Messengers: Identify second messengers produced in each system.

• Protein Kinase Activation: Learn which protein kinase is activated in both systems (PKA, PKC).

• Signal Termination Mechanisms: Understand how signaling effects are terminated.

Introduction to Metabolic Regulation

• Significance: Cells must receive and respond to environmental signals to regulate activities.

• Functions of Communication: Regulate metabolism and gene expression.

• Energy Balance: Links energy production with cellular demands to maintain survival.

• Coordination: Effective communication system is crucial for metabolic coordination in multicellular organisms.

Example: Glucose Homeostasis

• Processes:

  • Increase Blood Glucose: Signaled by Glucagon during low blood glucose levels.

  • Decrease Blood Glucose: Triggered by Insulin, promoting glucose uptake and synthesis.

• Homeostasis: Balance between glycogen degradation (high blood sugar) and glycogen synthesis (lower blood sugar).

Signal Transduction

• Definition: The process where intercellular signals (from one cell to another) become intracellular signals within target cells.

• Nature of Signals: Most signals are chemical.

Intercellular Signals

• Means of Communication:

  • Synaptic: Signals transmitted through neurons.

  • Endocrine: Hormonal signaling through the bloodstream.

  • Direct Contact: Physical connections between cells.

Intracellular Signals

• Receptor Roles: Receptors work as signal transducers, activating signaling molecules upon signal binding.

• Example: Activation can lead to an increase in cAMP production.

Steps in Signal Transduction

1. Synthesis and Release: Signaling molecule produced in response to stimulus.

2. Transport: Signal travels to target cell.

3. Reception: Signal binds to receptor protein on the target cell.

4. Generation of Intracellular Signal: Activated receptor produces an intracellular response.

5. Response: The target cell executes an appropriate action based on the signal received.

6. Termination: End signal to prevent overstimulation.

Types of Signaling Receptors

• Cell Surface Receptors:

  • Structure: Two domains (extracellular and intracellular).

  • Function: Bind peptide hormones (e.g., insulin, epinephrine) which cannot enter cells.

• Intracellular Receptors:

  • Location: Inside the cell (cytoplasm/nucleus).

  • Function: Bind steroid hormones (e.g., estrogen) that can pass through the membrane.

General Features of Signal Transduction

• Specificity: Correct signal molecule fits with the appropriate receptor.

• Desensitization/Adaptation: Receptor activation leads to feedback that can deactivate or remove receptors.

• Amplification: Signal cascades increase the number of affected molecules exponentially.

• Integration: Receptor input synthesizes the resultant signaling pathway.

Four General Types of Receptors

1. Steroid Receptors

2. Receptor Enzymes

3. Gated Ion Channels

4. G Protein Coupled Receptors (GPCRs)

Types of Receptor Mediated Signal Transduction

• For each receptor type, examples and functions are outlined, with a focus on location and mechanism:

  • Gated Ion Channels: e.g., Nicotinic Acetylcholine Receptors.

  • Steroid Hormones: Androgen and Progesterone receptors that regulate gene expression.

  • Enzyme receptors (Tyrosine Kinase): Crucial for glucose metabolism via insulin receptors.

  • G-Protein Coupled Receptors: Receptors activated by neurotransmitters; involved in various systems throughout the body.

Mechanism of Steroid Receptors

1. Hormone binds to receptor; translocates to nucleus.

2. Alters gene transcription rates via hormone response elements.

3. Result: long-term cellular changes take place over hours/days.

Mechanism of Gated Ion Channels

• Neurotransmitter binding opens channel, changes membrane potential impacting nerve impulses.

Receptor Enzyme Signaling

1. Ligand binds to receptor, initiating autophosphorylation of Tyrosine Kinase.

2. Series of phosphorylation events cascades through signaling pathways.

G-Protein Coupled Receptor (GPCR) Mechanism

• Structure: Seven transmembrane helices with binding sites.

• Activation leads to GDP-GTP exchange, triggering intracellular signaling.

GCPRs and Intracellular Second Messengers

• Two main systems via GPCRs:

  1. Adenylate Cyclase System (cAMP production).

  2. Phosphatidylinositol System (IP3, DAG production).

Summary of GPCRs Key Components

• Adenylate Cyclase: Activated by glucagon; generates cAMP, activating Protein Kinase A (PKA).

• Phosphoinositide: Activated by norepinephrine; produces IP3, DAG, activating Protein Kinase C (PKC).

Termination of the Signal

• Mechanisms: Removal of ligand, receptor deactivation, degradation of second messengers, reversal of phosphorylation events.

Final Summary

• Key points highlight the significance of effective cell-cell communication, the processes involved in signaling molecules, types of receptors, and the pathways leading to a cellular response.