Week 4 A - Cells and Immunity: Pathways Regulating Survival, Growth, and Proliferation

Course Overview

• Lecture Title: Cells and Immunity: Pathways regulating survival, growth, and proliferation
• Instructor: Mike Fry
• Date: October 2022
• Focus Areas:
  • Cell proliferation
  • Cell growth
  • Cell division
  • Cell survival

Key Concepts in Cell Signalling

• Molecular Recognition:
  • Specific interactions between molecules in signal transduction processes.
• Molecular Switches:
  • Includes G proteins and phosphorylation events.
• Signal Amplification:
  • Mechanism where a single signal triggers a large response within the cell.
• Second Messengers:
  • Molecules that relay signals from receptors on the cell surface to target molecules inside the cell.

Simple Cell Signalling Scheme

• Cells integrate signals from their environment to produce appropriate responses.
• Possible responses include:
  • Survive
  • Divide
  • Differentiate
  • Die (apoptosis or senescence)

Coincidence Detection

• Mechanism of signal integration where multiple signals must be present for a response.
  • Example: Blocking either signal 1 or signal 2 results in no output.

Signal Integration for Cellular Response

• Ras MAP Kinase Pathway:
  • Integrates multiple signals for diverse cellular responses like apoptosis and cell division.
• PI 3-Kinase/Akt Pathway:
  • Also integrates multiple signals favoring cell survival and growth.

Cell Cycle Overview

• Phases of Cell Cycle:
  • G1: Cell growth and preparation for DNA synthesis.
  • S-phase: DNA replication.
  • G2: Preparation for mitosis.
  • Mitosis (M): Division into two daughter cells.
• Checkpoints:
  • G1 Checkpoint: Checks if conditions are favorable for division.
  • S Checkpoint: Ensures complete DNA replication.
  • G2 Checkpoint: Prepares for mitosis.
  • M Checkpoint: Ensures proper chromosome alignment.

Cyclin/CDK Control Points

• Cyclins & CDKs:
  • Cyclin D/CDK4 and CDK6: Regulates G1 phase.
  • Cyclin E/CDK2: Transition from G1 to S phase.
  • Cyclin A/CDK2 & Cyclin B/CDK1: Cyclins involved in S phase and mitosis.

Phosphorylation in Cell Signalling

• Definition:
  • The addition of a phosphate group (PO4 2-) to proteins mediated by kinases.
  • Removal of phosphate by phosphatases.
• Phosphorylation Cycle:
  • Rapid and reversible process involving kinase and phosphatase activity.

Types of Protein Kinases

• Serine/Threonine Kinases:
  • Target serine and threonine residues.
• Tyrosine Kinases:
  • Target tyrosine residues; play crucial roles in signal transduction pathways.

Cellular Signalling Complexes

• Effector Systems:
  • Proteins activated by ligand-stimulated receptors that influence intracellular signaling.
• Adaptor Proteins:
  • Organize signal transduction complexes and mediate interactions between signaling proteins.

Molecular Switches

• GTP-binding Proteins:
  • Act as molecular switches involved in signal transmission.
• Phosphorylation Switches:
  • Activation or deactivation of proteins through phosphorylation.

Signal Amplification Mechanism

• Ras-MAP Kinase Cascade:
  • Activates multiple kinases in sequence leading to enhanced cellular responses.
  • Each activated kinase can amplify the signal significantly (e.g., if Raf activates 10 MEK, and each MEK activates 10 ERKs, total amplification can reach 10,000-fold).

Role of Myc Gene in Cell Cycle Regulation

• Myc Expression:
  • Regulates cyclin D expression, influencing cell cycle progression.
  • Excess Myc can lead to cell cycle arrest or apoptosis via p53 pathway activation.

Conclusion and Next Steps

• Upcoming lectures will address how growth and survival pathways integrate with Ras-MAPK signaling.
• Suggested Readings:
  • "Molecular Biology of the Cell" (Alberts) - Chapter 15 on cell communication.