Signal Transduction and Cytoskeleton

Adapter Proteins and Signaling Pathways

• Adapter Proteins
  • Bind to phosphorylated tyrosines on receptor tyrosine kinases (RTKs).
  • Activate downstream signaling pathways by facilitating the interaction with small GTPases like RAS.

RAS and GTPase Function

• RAS
  • A small GTP-binding protein involved in cell signaling.
  • Overexpressed in some cancers.
  • Activation occurs through a guanine nucleotide exchange factor, leading to the dissociation of GDP and the association with GTP.
  • This activation enables RAS to trigger kinase activity and affect downstream signaling pathways.

Signal Transduction Overview

• Signal transduction represents the process of relaying signals from outside the cell to the target proteins, ultimately affecting gene expression and protein activity.
• Key Process:
  • One signaling molecule activates another, leading to a cascade effect.

MAP Kinase Pathway

• MAP Kinase Cascade
  • Consists of three kinases:
  1. MAP kinase kinase kinase (often referred to as MAPKKK)
  2. MAP kinase kinase (MAPKK)
  3. MAP kinase (MAPK)
  • The cascade activates various downstream proteins altering their functions, including gene transcription.
  • This three kinase structure is due to evolutionary adaptation, allowing complex signaling.

Importance of Crosstalk in Signaling

• Crosstalk between Pathways:
  • Pathways integrate and coordinate responses through interactions.
  • Can enhance or inhibit signals depending on the combination of activations from multiple receptors.

Roles of Kinases and Phosphatases

• Kinases
  • Enzymes that phosphorylate proteins, usually activating them.
• Phosphatases
  • Enzymes that remove phosphate groups, often leading to protein inactivation.
• Phosphorylation can either activate or inhibit downstream proteins depending on the context within signaling pathways.

Signaling Molecules and Pathways

• Signal Molecule
  • Commonly referred to as a ligand that binds to its specific receptor, initiating a signaling cascade.
• Receptor Tyrosine Kinases (RTK) & GPCRs:
  • The two primary types of membrane receptors that activate various intracellular signaling pathways.

AKT Pathway

• AKT (Protein Kinase B)
  • Activated by a phosphoinositol 3-kinase (PI3K) that is recruited and activated through RTK phosphorylation.
  • AKT phosphorylates target proteins involved in cell survival, metabolism, and growth regulation.
• Cell Survival vs. Apoptosis
  • Signals that prolong survival through AKT can lead to the inactivation of pro-apoptotic factors (e.g., BAD protein) thereby inhibiting apoptosis.

Differential Effects of Signals

• Integrating Signals:
  • A cell can integrate signals based on the strength and duration of each signal, thus determining the resultant cellular response.
• Signals can have antagonistic effects, dictating cellular activities such as growth, protein synthesis, or programmed cell death (apoptosis).

Intracellular Receptors

• Nuclear Receptors:
  • Bind to hydrophobic signaling molecules like steroid hormones (e.g., cortisol, estrogen).
  • Function inside the cell, often within the nucleus, acting to regulate gene expression once bound to ligands.
  • These receptors may be cytosolic or nuclear and mediate signaling for a wide range of steroid hormones.

Conclusion

• Signal Transduction Summary:
  • The overall aim of signaling pathways is to regulate either gene expression or protein function leading to diverse cellular responses.
• Understanding both adapter proteins and specific pathways such as MAP kinase and AKT is essential for grasping cellular communication and regulation.