1. Bruno Sopko

2.  Signal Transduction Pathways  Organization  Signals  Receptors ◦ Soluble Receptors ◦ Transmembrane Receptors  Enzyme Coupled Receptors  G-Protein Coupled Receptors  Ion-Channel Coupled Receptors  Second Messengers, Amplifiers, Integrators  Response Changes to Signals  Inhibitors Content

6.  Soluble Receptors  Transmembrane Receptors ◦ Enzyme Coupled Receptors ◦ G-Protein Coupled Receptors ◦ Ion-Channel Coupled Receptors

7. Cortisol (glucocortikoid)Androsteron (steroid) All-trans retinol acid (retinoid) Vitamin D 2 3,3',5-trijodo-L-thyronine (thyroid)

9.  Tyrosine kinases phosphorylate protein tyrosine residues using ATP.  Phospholipase C cleaves PIP 2 into IP 3 and DAG.

12. JAK – Janus Kinase STAT – Signal Transducer and Activator of Transcription

13. Cytokins mostly

15. Charakteristic receptor structure Heptahelical receptors (7 transmembrane α-helixes)

18.  cAMP  cGMP  Phospholipids and Ca 2+  PI 3 kinase/AKT and mTOR  MAP kinase pathway

27.  Each MAP kinase Pathway starts with activation of Guanine Nucleotide Exchange Factor or GEF.In this example we see activation of GEF by T cell Adapter protein LAT,which links the ligand binding to the T cell receptor with MAP kinase pathways.  GEF proteins activates small G protein by exchanging GDP bound G protein for GTP.In the GTP bound state the G protein is active and can activate other proteins.  In the MAP kinase pathways the protein activated by small G protein is the MAP Kinase kinase kinase or MAPKKK.  The activated MAPKKK now phosphorylates a second kinase MAP kinase kinase or MAPKK.  MAPKK is a dual function kinase able to phosphorylate both tyrosine and serine on its target  MAPKK phosphorylates and activates third kinase called MAP kinase or MAPK.  Activated MAP kinase now migrates to the nucleus where its able activate transcription factors.

28.  Intracellular Phosphorylation sites  Receptor number – downregulation  Hormone-receptor complex taken into cell by endocytis  Degradation and recyclation of receptors  Number of available receptors can be altered by other hormones

29.  The chemical messenger itself (acetylcholine esterase, insulin degradation in liver)  The reaction itself (when GTP in G-protein is used, G-protein GDP complex forms the original structure)  Degradation of second messenger (phosphodiesterase cleavage of cAMP)  Phosphatases

30.  R.K. Murray et al.: Harper's Illustrated Biochemistry, twenty-sixth edition, McGraw-Hill Companies, 2003  Allan D. Marks, MD: Basic Medical Biochemistry a Clinical Approach, Lippincott Williams & Wilkins, 2009  Ernst J. M. Helmreich, The Biochemistry of Cell Signalling, Oxford University Press, USA, 2001  Geoffrey M. Cooper, Robert E. Hausman, The Cell: A Molecular Approach, Fourth Edition, Sinauer Associates, Inc., 2006  Michael J. Berridge, Peter Lipp and Martin D. Bootman, The versatility and universality of calcium signalling, Nature Reviews | Molecular Cell Biology (1), 2000