Syllabus
Key characteristics of cellular signaling networks are explained at the beginning of the course (1.-15.) and illustrated on the examples covered in subsequent lectures (A.-I.).
1. Receptors couple ligand-binding and effector specificity2. Signal is amplified on its way from receptor to effector3. Signal transduction pathways converge, diverge, form nodules and interact with each other - crosstalk4. Signal is transduced with the help of reversible posttranslational modifications and recognition codes5. Change in proximity of signaling molecules is itself an important signal6. Regulated folding and specific proteolysis can be used to transduce signals7. Signal transduction is compartmentalized using membranes and protein skeletons8. Information is transduced through both the amplitude and the frequency of messenger concentration changes9. Signal components are highly mobile molecules10. Complexity of signaling networks is achieved through combination of limited sets of elements11. Cell responses to signals have cooperative character12. Response to signal is always cell- and signal-context dependent13. Quantity changes in signaling networks can lead to quality changes in cell responses14. Signaling network robustness helps to distinguish signal from noise15. Effector systems of the cell form one integrated network. Outlines of signaling networks are explained; structure-function relationships of signaling proteins are presented.A. cAMP – protein kinase A – CREBA1. Protein kinase A structure-functionA2. PKA – CREB signalingA3. Modularity in signalingB. MAP kinase cascades – from mitogenic signals and stressors to Jun/Fos activationC. Insulin receptor - PI3Kinases - PKB - FoxO transcription factorD. GSK3 in PKB and Wnt signalingE. Nuclear hormone receptorsE1. Receptor structure-functionE2. Coregulators, SREMs, chromatin environmentF. Tumor suppressor p53 – from genotoxic stress to the p53 oscillator and the activation of p21 geneG. TGFβ signaling and CDK inhibitors – sensing gradientsH. NFκB/Rel pathways – two modalities of ubiquitin signalingI. Myc/Max – pRb – E2F transcription factors – Myc as a regulator of transcription pausing.
Annotation
The lectures can be given in English.
Protein-protein and protein-DNA interactions play central roles in signal and energy transduction within the cell. In the first part, the course reviews principal signaling pathways such as calcium and phospholipid signaling, trimeric G-protein coupled signaling, MAPK cascades, or growth factor receptor signaling, among others. In the second and main part, important classes of regulatory proteins are presented in more detail, illustrating the structure-function relationship, significance for oncogenesis, and latest advancements in the field. Major topics: Protein serine kinases, protein tyrosine kinases, lipid kinases, phospholipases, adenylate and guanylate cyclases, protein domains important in signaling, growth factor and cytokine receptors, adaptor proteins, small G proteins, MAPK cascades, focal adhesion signaling, important classes of transcription factors and their modes of regulation, coactivators of transcription factors, complexes for modification and remodeling of chromatin, preinitiation complex of RNAPolII, nuclear structure and gene expression.