1. Ch26 Cell Signalling Yuki Juan NTU May 19, 2003

2. Outline Introduction What are the singalling molecules Intracellular receptor-mediated responses Membrane receptor-mediated singalling systems Tyrosine kinase-associated receptors The G-protein-coupled receptors Singal transduction pathway using cGMP as second messenger

3. Outline Introduction What are the singalling molecules Intracellular receptor-mediated responses Membrane receptor-mediated singalling systems Tyrosine kinase-associated receptors The G-protein-coupled receptors Singal transduction pathway using cGMP as second messenger

4. Term Definition Second messengers:  A small intracellular regulatory molecules which causes cell responses.  E. g. Cyclic AMP

5. Outline of Receptor-mediated Signalling Target cell receptor

6. Cellular Responses to Singals

7. Outline Introduction What are the singalling molecules Intracellular receptor-mediated responses Membrane receptor-mediated singalling systems Tyrosine kinase-associated receptors The G-protein-coupled receptors Singal transduction pathway using cGMP as second messenger

8. What Are The Singalling Molecules Neurotransmitters Endocrine Howmones: (Table 26.1)  The “classical” singalling molecules Growth factors and cytokines  Regarded as singals Which may induce cell growth and division or inhibit it May affect differentiation Instruct the cell to undergo apoptosis Vitamins A and D derivatives  Retinoic acid (Vit A): singalling molecule in embryonic development and normal cell growth  Vitamin D 3 : control of genes involved in calcium absorption from the intestine

9. How Hormone Binding To Surface Receptor

10. Growth Factors and Cytokines Most cytokines/growth factors are paracrine, some are autocrine The first known growth factor was platelet- derived growth factor (PDGF)  PDGF stimulates cell division and repair Epidermal growth factor (EGF)  stimulates the growth of Skin cells Colony stimulating factors (CSFs)  Stimulate the growth of colonies of white cells on the culture plates.

11. Autocrine Singals and Paracrine Signals Autocrine signals affect the cell producing them. Paracrine singals diffuse only a short distance to affect nearby cells

12. Outline Introduction What are the singalling molecules Intracellular receptor-mediated responses Membrane receptor-mediated singalling systems Tyrosine kinase-associated receptors The G-protein-coupled receptors Singal transduction pathway using cGMP as second messenger

13. The Structures of the Lipid-soluble signalling Molecules They can combine with their specific receptors which exist inside the cell rather than in the membrane

14. Gene Activation by Steroid Hormones The glucocorticoid receptor: one of a superfamily of steroid/thyroxine receptors Binding to DNA sites by zinc fingers

15. Outline Introduction What are the singalling molecules Intracellular receptor-mediated responses Membrane receptor-mediated singalling systems Tyrosine kinase-associated receptors The G-protein-coupled receptors Singal transduction pathway using cGMP as second messenger

16. Central Principle of Control by Many Extracellular Signals Key processes in cell signalling are protein phosphorylation by protein kinases and reversal by protein phosphatases

17. Tyrosine Phosphorylation by Tyrosine Kinase

18. Tyrosine Kinase Type of Receptors and The Other Type of Signalling Adaptor molecules

19. Outline Introduction What are the singalling molecules Intracellular receptor-mediated responses Membrane receptor-mediated singalling systems Tyrosine kinase-associated receptors The G-protein-coupled receptors Singal transduction pathway using cGMP as second messenger

20. Tyrosine Kinase-associated Receptors Ras signal transduction pathway  Ras : a protein exits in all eukaryotic cells  There are no small molecular weight second messengers in this pathway—all of the components are proteins  Ras was discovered as the oncogenic protein coded for by the rat sarcoma virus Phosphatidylinositide 3-kinase pathway JAK/STAT protein-associated receptor

21. The Ras Singal Transduction Pathway Raf, MEK and ERK: mitogen- activated protein kinases (MAP) kinases Raf: rat sarcoma; MAPKKK MEK: Map kinase/ERK; MAPKK ERK: extracellular siganl- regulated protien kinase; MAPK

22. The Ras Singal Transduction Pathway

23. The Control of The Ras Protein

24. A Rapid Molecular Switch Mechanism

25. Multiple Signal Pathways Of The Ras Type

26. Phosphatidylinositide 3-kinase Pathway PI 3 kinase involved in  Cell proliferation  Differentiation  Other cellular activities including metabolic control Insulin

27. Simplified Insulin Singalling Pathway IRS: insulin receptor substrate PKB: protein kinase B

28. Production of The Second Messenger

29. JAK/STAT Protein-associated Receptor Interferons  A protective proteins released by cells infected by virus STAT proteins  Singal transducer and activator of transcription  SH2 domains bind to the phosphorylated receptors JAK kinase:  Janus kinase  Has two catalytic sites

30. The Singalling Pathway by Which  - interferon Activates Specific Gene Transcription

31. Outline Introduction What are the singalling molecules Intracellular receptor-mediated responses Membrane receptor-mediated singalling systems Tyrosine kinase-associated receptors The G-protein-coupled receptors Singal transduction pathway using cGMP as second messenger

32. The G-protein-coupled Receptors G protein:  Heterotrimeric  A protein made up of three different subunits: , ,  G protein receptor have no enzymic activity

33. The Structure of The  2 -adrenergic Recptor

34. cAMP

35. The Control of Adenylate Cyclase Activity by a Hormone Such As Epinephrine

36. The  2 -adrenergic Recptor Function PKA: protein kinase A CREB: cAMP response element binding protein CRE: cAMP response element of gene promoter

37. Hydrolysis of Phosphatidylinositol-4, 5- bisphosphate

38. The Phosphatidylinositol Cascade

39. Phorbol Esters Tumor-promoting effect

40. Structure of a Rod Cell

41. The Structures of Light Singal Molecules

42. The G-protein-coupled Receptor Involved In Vision

43. Simplified Diagram of The Visual Process

44. Outline Introduction What are the singalling molecules Intracellular receptor-mediated responses Membrane receptor-mediated singalling systems Tyrosine kinase-associated receptors The G-protein-coupled receptors Singal transduction pathway using cGMP as second messenger

45. Formation of 3 ’,5 ’– cyclic GMP

46. Production of The Second Messenger cGMP by Two Routes

47. Simplified Summary Diagram of The Singal Transduction Pathways

48. Ch28 Virus and Viroids Yuki Juan

49. Virus Much smaller It generates no energy and catalyses no reactions Structure simple  Genetic materials: DNA or RNA  Protein 病毒的區分  依外觀區分  依遺傳物質區分

50. How Are Virus Get Into Cells ? The receptor-mediated endocytosis

51. Bacterial Virus (Bacteriophages)

52. Types of Genetic Material in Different Virus Double-stranded DNA Single-stranded DNA Double-stranded RNA Single-stranded RNA  (+)sense RNA  (-)non-sense RNA

53. Why can some virues get away with having RNA as genetic material That viral genomes are exceeding small  therefore the chances of deleterious mutations during replication of viral RNA are smaller. Rapid mutation helps the virus to escape immunological attack by the animal host.

54. Double-stranded DNA Viruses Transcribed by host RNA polymerase

55. Double-strand RNA Viruses RNA-dependent RNA polymerases Translation by the host cell machinery

56. Single-stranded RNA Viruses  (+)sense RNA (HIV) The protein synthesizing machinery of the cell can immediately translate it into proteins  (-)non-sense RNA An additional RNA-replicating enzyme is needed

57. Release of Viral Particles

58. Vaccinia Double-stranded DNA viruses Own RNApolymerase

59. Polioviurs Naked virion: it has only a nucleocapsid shell of coat protein but no membrane) (+)single-strand RNA Producing an RNA replicase Polyprotein: a single largeprotein

60. Influenza virus (-) strand RNA virus

61. Retrovirus

62. Bacteriophage lambda