1. Chapter 11

2. Signaling Types  Two main types  Local signaling  Also called paracrine signaling  Influence cells in the local vicinity  Ex. Growth factors, synaptic signaling  Long distance signaling  Use of hormones (endocrine signaling)  Nervous system impulses can be considered long distance  How do you determine if a cell will respond to a specific signal?

3. Stages of Cell Signaling  Stages of signaling  Reception  Transduction  Response

4. Sutherland Experiment  Question: How does epinepherine stimulate glycogen breakdown in the liver and skeletal muscles?  Discovered ephinepherine simulates glycogen breakdown by cystolically producing glycogen phosphorylase  Problem: When glycogen added to a test tube with enzyme no breakdown occurred-only worked when added with complete cells

5. Reception  A signal molecule must receive the signal and respond  Molecule must fit the shape of the receptor  Signaling molecule is called a ligand  Most receptors are membrane proteins  Three types of membrane receptors  G protein-coupled receptors  Tyrosine kinases  Ion channel receptors

6. G protein-coupled receptors  G protein acts as a switch  Depends on which molecule is attached – GDP or GTP  Work with another protein-usually an enzyme  Signal causes GTP to displace GDP  G protein leaves receptor and binds to enzyme  G proteins also functions as GTPase – breaks down GTP to GDP-inactive  G protein leaves the enzyme and starts again

7. Tyrosine Kinase Receptor  Begin as individual units with tyrosine units internally  Signal molecule cause two receptors to come together – dimer  Activates tyrosine kinase-adds a phosphate to the tails  Once activated specific relay molecules bind and cause a cellular response

8. Ion Channel Receptors  Gate is closed until the signal molecule attaches  Once attached the channel opens and specific ions can flow  This can induce a cellular response  Once it detaches the gate closes  Ex. Action potentials

9. Intracellular receptors  Found within the cytoplasm or nucleus  Have to be able to pass through the membrane  Ex. Steroids, thyroid hormones, NO  Cells must have the receptor internally to respond  Binds to a receptor protein  Protein and hormone enter nucleus-turn on specific genes

10. Transduction  Usually several steps  Allows for control and amplification  Receptor molecule activates relay molecules  Usually proteins  Protein kinases transfer phosphate from ATP  Protein phosphatases remove phosphates

11. Transduction  Other molecules can act in the transduction pathway-Second Messengers  Typically ions or small, water soluble molecules  Ex. cAMP or Ca 2+

12. Cyclic AMP  Signaling molecule activates GPCR which activates a G protein  G protein activates adenylyl cyclase  Converts ATP to cAMP  cAMP acts on a protein kinase  Phosphorylation of proteins occurs  Cellular response occurs

13. Calcium ions and IP 3  Increase the cytostolic concentration of Ca 2+  Ex. Neurotransmitters, growth factors, hormones  Results in muscle contraction or cell division

14. Calcium ions and IP 3  Signal stimulates G protein  G protein cleaves a phospholipid  DAG and IP 3  IP 3 diffuses through the cell to gated Ca 2+ gated channels  Channels open  Ca 2+ flows out of ER  Increase in Ca 2+ concentration stimulates next protein in path

15. Response  Response is either in the cytoplasm or the nucleus  May act as a transcription factor in the nucleus  May cause the opening/closing of ion channels

16. Response  Fine tuning the response involves:  Amplification  Results for multiple steps in the sequence increasing the strength of the signal  Specificity  Multiple steps allow for coordination of the response at various steps which can increase specificity  Efficiency  Scaffolding proteins increase the efficiency of the response  Termination  The ability to turn off the signal

17. Signal Amplification  The number of products at each step is greater than the one before  Occurs because relay proteins stay in the active stage longer and thus can activate more of the next molecule

18. Specificity  Many cells are exposed to the same signal but don’t respond or have different responses – why  Different cells have different proteins which respond differently to same signal

19. Efficiency  Signal efficiency is increased by scaffolding protiens  Large relay proteins with several other relay proteins attached  This brings the signaling proteins closer so the signal is more efficient

20. Termination  Signal molecule binding is reversible  As the concentration falls below threshold, the resp0nse ceases  Relay molecules return to the inactive stage

21. Apoptosis  Programmed cell death  Infected, diseased, damaged cells undergo this  Cell DNA/organelles are cut up, packaged, digested  No trace they ever existed

22. Apoptosis  Signal originates outside the cell  “Death signal”  Usually released from another nearby cell  Binding leads to activation of enzymes that carry out apoptosis  Can also originate from inside the cell