SUBJECT
Receptors, Signal Transduction, Cell-cell Communication
lecture
master
3
Semesters 1-4
Autumn/Spring semester
1-2. Introduction.
Hydrophobic and hydrophilic ligands, autocrin, paracrin, endocrin signaling, intracellular and cell surface receptors, diffusible second messengers, protein-protein interactions, G-protein type switches, effectors. Agonists, inverse agonists, antagonists. Spatial organization of the signaling system: anchoring and network-forming molecules/modules. Receptor-mediated processes: metabolic and cytoskeletal changes, proliferation and apoptosis. Regulation of signal specificity, strength, type, dynamics, amplification, adaptation, switching off. Receptor networks and interactions.
3-4. G-protein mediated signaling pathways.
Structure of heterotrimeric G-protein coupled receptors (GPCR), types of heterotrimeric G-proteins, GPCR signaling (second messengers, kinase activation), anchoring (AKAP) proteins. Mechanisms of adaptation: GRK, arrestin, RGS, endocytosis.
5. Calcium signaling.
Mechanisms of oscillattion, ryanodin and inositol- trisphosphate receptors, calcium pumps, CaM kinase, calcineurin/NFAT.
6-7. Receptor-protein tyrosine kinases.
Growth factors, receptor-protein tyrosine kinases, Ras-MAP kinase and stress-activated kinase systems. Phosphatidyl-inositol kinase signaling, regulation and function of the AKT/TOR system.
8. Cytokine signaling.
Cytokines as humoral factors regulating the immune system. Types of cytokines, JAK/STAT signaling.
9. Morphogene signaling.
Receptor-serine/threonine kinases, morphogenes (TGF-beta, BMP). SMAD phosphorylation, role of the R-SMAD/co-SMAD complex in regulating transcription.
10. Dependence receptors.
Netrin-DCC/Unc5 signaling. Role of dependence receptors in cell death and metastasis.
11-12. Signaling pathways involved in development.
WNT/beta-catenin, Notch, Hippo, Hedgehog signaling mechanisms.
13. Cell death signaling.
Signaling pathways involved in apoptosis. Receptor-mediated (extrinsic) and cytoplasmic (intrinsic) activation routes.
14. Nuclear receptors.
Signal transduction by lipid-soluble ligands, transcription changes induced by nuclear receptors.
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Bastien D. Gomperts, Ijsbrand M. Kramer, Peter E.R. Tatham: Signal Transduction, 2nd ed., Academic Press, 2009
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Michael Friedman, Brett Friedman: Cell Communication, The Rosen Publishing Group, 2005