1. Chapter 16
Cell Communication

2. 1. General Principles of Cell Signaling
1) Signal can act over long or short range
(1) Ways to contact

3. (2) Contrast between endocrine and synaptic signaling

4. (2) Gap junctions allow signaling information to be shared by neighboring cells

5. (1) Animal cell depends on multiple extracellular signals
2) Each cell responds to a limited set of signals
(1) Animal cell depends on multiple extracellular signals

6. (2) Same signal can induce difference response in different target cells

7. 3) Receptors relay signals via intracellular signaling pathways
(1) Extracellular signals alter the activity of a variety of cell proteins to change the behavior of the cells

8. (2) Cellular signaling cascades

9. 4) Nitric oxide crosses the PM and activates intracellular enzyme directly
(1) Extracellular signal molecules bind either to cell-surface Rs or intracellular enzyme or Rs

10. (2) Examples of NO actions
NO triggers smooth muscle relaxation in a blood-vessel wall
NO activates guanylyl cyclase

11. 5) Nuclear Receptors are ligand-activated gene regulatory proteins
(1) Some small hydrophobic hormones bind to intracellular Rs that act as gene regulatory proteins

12. (2) Nuclear Receptors superfamily
Receptors all have a related st.

13. The binding of ligand to the receptor cause the activation of receptors

14. Response induced by the activation of a nuclear hormones receptor

15. 6) Cell-surface Rs fall into 3 main classes

17. 7) Intracellular Signaling molecules
(1) Most activated cell-surface receptors relay signals via small molecules and a network of intracellular signaling proteins

18. (2) Many intracellular signals proteins act as molecular switches

19. (3) Intracellular signaling complex enhance the speed, efficiency, and specificity of the response

20. (4) Interaction between intracellular signaling proteins are medicated by modular binding domains

21. 8) Cells can adjust their sensitivity to a signal

22. 2. G-protein-linked receptors
Inactive G protein

23. (1) G protein dissociate into two signaling proteins when activated
1) Stimulation of G-protein -linked Rs activates G-protein subunits
(1) G protein dissociate into two signaling proteins when activated

24. (2) G-protein α subunit switches itself off by hydrolyzing its bound GTP

25. 2) Some G proteins regulate ion channels

26. 3) Some G proteins activate membrane-bound enzyme
(1) G protein activate adenylyl cyclase
Adenylyl cyclase

27. (2) cAMP concentration rises rapidly in response to an extracellular signal

28. (3) Extracellular signaling can act slowly or rapidly

29. Example of
slow response

30. 4) IP (inositol phospholipid ) pathway triggers a rise in intracellular Ca2+
Hydrolysis of PI by PI kinase and phospholipase C

31. IP3 pathway

32. 5) Ca2+ Signal triggers many biological processes
(1) Fertilization of an egg by a sperm triggers an increase in cytosolic Ca2+ in the egg

33. (2) [Ca2+ ] in the cytosol is extremely low
Main ways eucaryotic cells maintain a very low concentration of free Ca2+ in their cytosol

34. (3) Effect of Ca2+ in the cytosol are largely indirect
Ca2+/calmodulin

35. Activation of CaM-kinase II

36. Rod photoreceptor cell from retina
6) Intracellular signaling cascades can achieve astonishing speed, sensitivity, and adaptability: A look at photoreceptors in the eye
Rod photoreceptor cell from retina

37. Light-induced signaling cascade in rod photoreceptor cell greatly amplifies the light signal

38. 3. Enzyme-linked Rs 1) Receptor tyrosine kinases
(1) Phosphorylate themselves
7 superfamily of receptor tyrosine kinases

39. (2) Activated R tyrosine kinases assemble a complex of intracellular signaling protein

40. (3) Inhibition of signaling through normal receptor tyrosine kinases by an excess of mutant receptors

41. (4) Phosphorylated tyrosines serve as docking sites for proteins with SH2 domains

42. (5) R tyrosine kinases activate the GTP-binding protein Ras

43. Ras activates a MAP-kinases phosphorylation cascade

44. organization of MAP-kinases pathway by scaffold proteins in budding yeast

45. Jak-STAT signaling pathway activated by α-interferon
2) Cytokine receptors activate the Jak-STAT signaling pathway, providing a fast tract to the nucleus
Jak-STAT signaling pathway activated by α-interferon

46. 3) TGF-β superfamily signals along receptor serin/threonine kinase and smads

47. 4) Protein kinase network integrates information to control complex cell behavior

48. Example of signal integration

49. 3. Signaling pathway dependent on regulated proteolysis
1) Receptor protein notch is activated by cleavage
(1) Lateral inhibition mediated by Notch and Delta during nerve cell development in Drosophila

50. (2) Processing and activation of Notch by proteolytic cleavage

51. 2) Wnt binds to Frizzles and inhibit the degradation of β-catenin

52. 3) Hedgehog act through complex of Patched and smoothened

54. 4) Multiple stressful and proinflammatory stimuli act through an NF-kB dependent signaling pathway