1. I.Signal Transduction Pathways II.Signaling ranges III.Three receptor classes (families) IV.Intracellular receptors V.Phosphorylation cascades VI.Second messengers VII.Signal efficiency VIII.Apoptosis IX. Summary Lecture 8 Outline (Ch. 11)

2. Cell Signaling = Signal Transduction Signal Transduction – receiving a signal & relaying the response

3. Reception Transduction Response Receptor Relay molecules Signaling molecule Activation of cellular response 1 2 3 Signal Transduction Cell phone rings You listen to your friend You drive somewhere Response variable – examples: mate, organize, divide, die, grow, send another signal, etc…

4. Sending the Signal – direct contact

5. Sending the Signal Three methods of cell signaling over distances:

6. Signal Transduction Signaling-molecule binding site Segment that sends signal inside cell The receptor is a protein that detects the signal Signal called a ligand

7. G-protein coupled receptors (GPCRs) A 7-pass transmembrane receptor Links via a G-protein….binds GTP/GDP

8. Receptor Tyrosine Kinases (RTKs) Transmembrane receptor – dimerizes when activated Auto-phosphorylates when active to rely signal

9. Ligand-gated ion channels Open when the ligand is bound Close when signal is not present

10. Signal Transduction for hydrophobic molecules Receptor protein Hormone (testosterone) EXTRACELLULAR FLUID Plasma membrane Hormone- receptor complex DNA Hormone (testosterone) EXTRACELLULAR FLUID Receptor protein Plasma membrane Hormone- receptor complex DNA NUCLEUS CYTOPLASM hydrophobic signals - Receptor moves to DNA

11. Transduction – relay the signal Phosphorylation: adding a phosphate group Used to activate proteins already in the cell

12. Transduction hydrophilic signals – relay the signal Dephosphorylation = removing a phosphate group

13. Signaling molecule Receptor Activated relay molecule Inactive protein kinase 1 Active protein kinase 1 Inactive protein kinase 2 ATP ADP Active protein kinase 2 P P PP Inactive protein kinase 3 ATP ADP Active protein kinase 3 P P PP i ATP ADP P Active protein PP P i Inactive protein Cellular response Phosphorylation cascade i hydrophilic signals Receptor alerts molecules inside the cell = phosphorylation Signal Transduction for hydrophilic molecules

14. First messenger G protein Adenylyl cyclase GTP ATP cAMP Second messenger Protein kinase A G protein-coupled receptor Cellular responses Or use second messengers = small molecules inside cell to relay message example second messengers: GTP, cAMP, ATP, Ca++ Signal Transduction for hydrophilic molecules

15. Specificity of cell signaling

16. Scaffold proteins increase signal efficiency Scaffold protein – larger protein for binding and bringing together several other signal proteins

17. Interdigital tissue 1 mm Response – cell does something

18. protein (active) Inhibits activity Mitochondrion Receptor for death- signaling molecule Inactive proteins (a) No death signal Response – ex. No death signal, cell lives Apoptosis – programmed cell death - membrane inverts - biomolecules degraded - organelles break down

19. (b) Death signal Death- signaling molecule (inactive) Cell forms blebs Active Activation cascade Other proteases Nucleases Response – ex. Death signal, cell undergoes apoptosis Caspases

20. Growth factor Receptor Phosphorylation cascade Reception Transduction Active transcription factor Response P Inactive transcription factor CYTOPLASM DNA NUCLEUS mRNA Gene Signal transduction = reception, transduction, response