Lecture on Cytokine Receptors and Signaling Pathways

Overview

• Focus on cytokine receptors and principles of cytokine signaling.
• Specific pathways: JAK-STAT and interferon signaling.
• Effects of cytokine signaling.

Cytokine Signaling

• Pattern recognition receptors in host cells detect PAMPs.
• Activation of signaling pathways leads to protein activation.
• Transcription factors bind to DNA to express genes (cytokines, chemokines).
• Cytokines/chemokines released affect target cells with specific receptors.
• Mediate processes like inflammation and chemotaxis.

Cytokine Receptors

• Type 1 Cytokine Receptors: Utilized by hematopoietin cytokines.
• Type 2 Cytokine Receptors: Utilized by interferon cytokines.
• No intrinsic enzymatic activity but associated with Janus kinases (JAKs).
• TNF Family Cytokines: Bind to TNF receptor family.
• Interleukin-1 Family: Use immunoglobulin-type receptor family.
• Chemokines: Use G-protein-coupled receptor family.

JAK-STAT Pathway

• Initiated by cytokine binding and receptor dimerization.
• JAKs phosphorylate each other (trans-phosphorylation) and then phosphorylate receptors.
• Phosphorylated receptors form binding sites for STAT proteins (transcription factors).
• STAT proteins become active upon phosphorylation, form dimers, and bind DNA.
• Regulates gene expression important for immune cell growth and differentiation.
• Pathway needs regulation; constitutive activation linked to diseases like cancer.
• Deactivation by de-phosphorylation or blocking interactions.

Interferon Signaling

• Type 1 Interferons: Include IFN-alpha, IFN-beta; activate JAK-STAT pathway.
• Type 2 Interferons: Include IFN-gamma; also activate JAK-STAT.
• Type 3 Interferons: Include IFN-lambda.
• Activation leads to antiviral defense via interferon-stimulated genes (ISGs).
• Examples of ISGs:
  • IFI TM3: Prevents virus fusion to endosomes.
  • PKR: Suppresses protein translation.
  • OAS: Degrades viral RNA.

Cytokine and Chemokine Functions

• Influence differentiation, growth, and proliferation of cells.
• Cytoskeletal reorganization through actin polymerization and depolymerization.
• Regulation of immune cell production and function in response to pathogens.

Conclusion

• Overview of cytokine and chemokine receptors and their signaling pathways.
• Examined hematopoietin and interferon signaling pathways.
• Discussed outcomes of cytokine signaling, including immune cell regulation.