1. Ligand
    First messenger - Neurotransmitters & drugs
  2. Receptor proteins - ligand binds to?
    Ligand binds to multiple receptors
  3. What is a Binding site?
    Specific point of ligand & receptor
  4. Affinity
    • Attraction
    • Physical & electrical fit
  5. Ligands
    = neurotransmitters made by the brain
  6. Picture
    • Yellow = brain cell
    • Endocrine process
    • Endocrine system
    • Paracrine proces- cell makes signals to surrounding cells
    • Autocrine process � cell makes signals to itself
  7. Cell contains receptors, if the ligand fits, a cascade of chemical changes will occur to tell the DNA to make
    specific proteins, enzymes, or hormones
  8. Signal transduction
    passing of the message; message remains exactly the same
  9. The overflow of information during cell signaling
    • Hydrophilic signal � prinmary messenger � Hydrophobic signal
    • Plasma membrane Intracelllular receptor
    • Receptor:
    • Lined to protein kinase
    • Linked to g protein Signal proteins
    • a)Cyclic AMP
    • b)IP3, DAG, Ca2+ Second messenger
  10. Chemical Signaling Mechanisms
    • Synaptic
    • Paracrine
    • Medium range intercellular signaling
    • Endocrine
    • Hormones via blood
    • Pheromones
    • Via air ~
  11. Signaling Pathways:Cell impermeable requires?
    Requires receptor in membranes
  12. Signaling Pathways: Cell permeable
    • Lipid soluble
    • Steroid hormones
  13. Signaling Pathways: cell associated signaling molecules
    • Signal transduction pathway can amplify the cellular response on an external signal
    • Ligands
  14. Hydrophobic will pass through membrane and
    do not need receptor
  15. Hydrophylic will not pass
    needs receptors
  16. For hydrophobic ligand
    also need receptor for proteins
  17. Receptor Types: Channel linked receptors
  18. Receptor Types: Enzyme linked receptors
    • Protein kinase mostly
    • Neurotrophin � R
  19. Receptor Types:G protein �
    • coupled receptors
    • Metabotropic
  20. Receptor Types: Intracellular receptors
    Activated by cell � permanent signals
  21. Metabotropic receptors
    G Protein coupled receptors
  22. Metabotropic receptors Requires
  23. Metabotropic receptors: Receptor indirectly controls channel
    • G protein � gated ion channel
    • 2d messenger systems
  24. Metabotropic receptors: Neuromodulation
    • Slower action
    • Change in sensitivity of neuron
  25. G protein-gated Ion Channels: NT binds to
    receptor protein
  26. G protein-gated Ion Channels: NT binds to receptor protein which activates
    G protein
  27. 2d Messenger Systems NT is ?
    First Messenger --> Ligand Membrane --> associated componentsReceptorTransductionPrimary effector
  28. G protein binds to channel which does what?
    • opens or closes
    • relatively fast
  29. Intracellular
    • 2d messenger
    • Secondary effector
    • Slower & enduring changes
    • Multiple effectors
  30. Signal amplification
    • 1 NE � 1000s cAMP
    • 1000s cAMP � 10,000s phosphates
  31. 2d Messenger Systems: Effects
    • Control channel
    • Alter properties of receptors
    • regulation of gene expression ~
    • Calcium (Ca2+)
    • Target: calmodulin
  32. Calmodulin activates
    protein kinases & phosphatases
  33. Cyclic nucleotides cAMP & cGMP activates?
    • (Activates Kinases)
    • Target: protein kinases ~
    • Increased concentration cyclic AMP activates kinases
  34. The structure and metabolism of cAMP. cAMP is generated by
  35. The enzyme of cAMP is
    enzyme adenylyl cyclase
  36. 2d messenger: Diacylglycerol
    DAG --> protein kinase C (membranes)
  37. 2d Messengers: Membrane Lipids
    • Precursor PIP2
    • Phoshatidylinositol bisphosphate Cleaved by phosphylipase C
  38. cAMP It is inactivated by hydrolysis of AMP, a reaction catalyzed by
  39. 2d MEssenger: Inositol triphosphate
    • IP3 --> Ca2+ (ER) --> Frees Ca2+ from inside to outside
    • Diacylglycerol & Inositol triphosphate
    • Activates DAG ---> Protein kinase C and calcium
  40. IP3 is made from PIP2 as uncommon phospholipid membrane where the enzyme phoapholipase C is acivated. Phosphylipase C cleaves PIP2 into
    2 molecules of IP3 and DAG.
  41. Roles of IP3 and DAG as second messengers.
    • 1.Ligand binds to receptor
    • 2.G-Protein acication
    • 3.Gq activates phospholipase C that generates IP3 and DAG
    • Inositol triphosphate is water soluble. Diffusing through the cytosol and binding to a calcium channel known as IP3 receptor.
    • Then he channel opens releasing calcium to eh cytosol.
    • Calcium then elicits the desired physiological response.
  42. 2d Messenger Targets: Enzymes
    Modulate phosphorylation
  43. 2d Messenger Targets:: Protein Kinase
    • Activated by: Ca2+, CAMP, DAG, etc.
    • Increases phosphorylation
  44. 2d Messenger Targets: Protein Phosphatases
    • Decreases phosphoryation
    • Activated by Ca2+/Calmodulin
  45. The release of calcium ion and signal processes.
    Calcium plays an essential role in regulating cellular function
  46. The concentration of Ca is very low in the cytosol due to the presence of
    • calcium ATPases
    • There are several different ways that various stimuli can increase Ca in cytosol (neurotransmitter, fertilization of animal egg, egg activation etc.)
Card Set
Chapter 14 Signal transduction