1. Chapter 1111.3Pgs. 214-218 Objective: I can describe different transduction pathways, noting how specific molecules will turn on or turn off and identifying which enzymes do what activity.

2. Cell Signaling: Review Cellular “conversation” has 3 stages 1) Reception 2) Transduction: relaying signal through cell 3) Response

3. Transduction (basically means) Passing of information by transforming receiver (listener) into giver (speaker) Done through multiple “relay molecules” Allows for amplification Allows for more regulation & control (activate or repress at certain steps) Note: original signal molecule not physically passed along signal transduction pathway Note: most relay molecules are proteins which undergo conformational changes WHY?!?

4. Changing Relay Molecule Protein Most common conformational change = Phosphorylation  add phosphate (what type of protein adds phosphate?) Protein Kinases Differences from Receptor Tyrosine Kinase 1) Receptor tyrosine kinase phosphorylates itself 2) Phosphorylate serine or threonine (not tyrosine) Conformational change typically activates relay molecule (but may inactivate)

5. To activate NEXT relay molecule, phosphorylates through ATP (does NOT lose own phosphate)

6. Review of Protein Structure Why add phosphate causes shape change? Phosphate is polar, so it can attract polar A.A. and “repel” nonpolar A.A.

7. Review of Protein Structure Why add phosphate causes shape change? Phosphate is polar, so it can attract polar A.A. and “repel” nonpolar A.A.

8. Regulation of Phosphorylation For relay molecules kinases that are phosphorylating / being phorphorylated… Can dephosphorylate using enzymes called protein phosphatases Allows relay molecule to reset Can shut down system entirely Balance between kinase and phosphatase allows for an on/off switch of activity Note: if phosphorylating inactivates relay, need phosphatase to activate…

9. Other relay molecules(not protein) Second messengers Small, non-protein, water-soluble molecules or ions that act as relay in transduction of signal Can spread rapidly via diffusion in cell BECAUSE they are small/polar Two most common second messengers Cyclic AMP (a.k.a. cAMP) Calcium ions (Ca 2+ )

10. Cyclic AMP (cAMP) Adenylyl cyclase converts ATP into cAMP Phosphodiesterase converts cAMP into AMP cAMP can cause a response OR cAMP can activate a protein kinase (specifically, protein kinase A), which leads to a response (possibly through a relay)

11. Putting it together: Reception, Transduction Signal molecule G-protein linked receptor G-Protein Activate enzyme Adenylyl cyclase ATP  cAMP Protein Kinase

12. Regulation: Controlling if system on/off If signal molecule not bound… Still have cAMP to cause response… Phosphodiesterase quickly converts cAMP into AMP Needs MORE signal to bind if want response Also can inihibit adenylyl cyclase with an inhibitory G-protein Phosphodiesterase AMP GDP Inhibitory G-protein

13. Example Disease caused by malfunction in regulation Cholera caused by bacteria (drinking water contaminated by human feces) Signal pathway (w/ G protein) to secrete water/salt via adenylyl cyclase activating (prev. diagram) Bacteria toxin modifies G protein; can’t hydrolyze GTP back to GDP  keeps adenylyl cyclase active Cellular response is to secrete lots of water and salt  profuse diarrhea Leads to dehydration and death Medical drugs: viagra (read in book)

14. Calcium Ions (as Second Messengers) Ca 2+ more widely used than cAMP Muscle contraction! Ca 2+ pumps keep cytosolic/cytoplasm concentration low (extracellular and inside organelles high – 10,000 times )

15. How calcium ions released Other second messengers involved Inositol triphosphate (IP 3 ) Diacylglycerol (DAG) So, technically Ca 2+ is 3 rd messenger, but…

16. Review: Note the mix/match Reception (3 types) G-protein-linked receptors Receptor Tyrosine Kinases Ion Channel Receptors Transduction (2 types…then 2 specific ex.) Protein Kinase Relays (phosphorylation) Second messengers cAMP Ca 2+ ions