Cell Signaling S1M1

  1. Adenylate cyclase catalyzes the conversion of
    ATP to cAMP
  2. Targets of signaling cascades are
    • Enzymes
    • Membrane transporters & ion channels
    • Transcription
  3. Steroids enter the cell how
    Passive diffusion across the plasma membrane
  4. Glucocorticoids
    Are a class of steroid hormones that bind to the glucocorticoid receptor, which is present in almost every vertebrate animal cell
  5. Steroid receptors are unique with
    Zinc-finger proteins that function as ligand-activated transcription factors.
  6. What is the pathway for a steriod hormone into the cell
    The hormone diffuses across the membrane and binds its receptor in cytoplasm or nucleus.

    The hormone-receptor complex binds to response elements in the promoters and enhancers of genes.

    This stimulates transcription.
  7. The mechanism for steroid hormones is also used by:
    • Retinoic acid (vitamin A)
    • Thyroid hormones
    • Calcitriol (vitamin D)
  8. Testicular feminization is caused by
    A defective androgen receptor
  9. Androgen
    Steroid hormone that stimulates or controls the development and maintenance of male characteristics
  10. Coffee inhibits
    Phosphodiesterases (breaks phosphodiester bonds)
  11. A hormone receptor must do what when bonded by a signal molecule
    It must change conformation on the cytoplasmic or nuclear side
  12. Water soluble hormones must deliver their message where
    To the cell surface
  13. Cyclic AMP is synthesized
    From ATP and degraded to AMP
  15. A receptor protein always has how many alpha helices that span the membrane
  16. Once the GDP attaches to the receptor
    It changes to GTP (its active state)
  17. How does the GTP prevent from continually sending a signal once it has been triggered
    The alpha sub unit turns it off once it binds, turning it back to GDP by hydrolysationImage Upload 2
  18. What is the cascade of the cyclic AMP signaling pathway
    • 1. A receptor is activated by a signal
    • 2. The G protein is activated
    • 3. G protein activates Adenylate Cyclcase
    • 4. The G protein stops itself from signaling further
    • 5. The cyclic AMP activates the protein kinase
    • 6. The protein kinase goes around phophorilating proteinsImage Upload 4
  19. Inhibition of adenylate cyclase
    Is pretty much the same cascade as activating only the G protein inhibits the Adenylate cylcase instead of activating it. Both are functioning in the cell at the same time, one just is simply functioning at a higher rate
  20. What if there was no inhibition
    Then the cyclase would continue to happen without stopping
  21. Adenylate cyclases are triggered by what
    The alpha subunit of the G protein
  22. Cyclic Amp mediates the effects of many
  23. Cyclic adenosine monophosphate (cAMP, cyclic AMP) is
    A second messenger important in many biological processes
  24. What is Hormone resistance
    When a patient has the hormones, but the effects of the hormones are absent
  25. Pseudohypoparathyroidism
    Patient has signs of chronic PTH (parathyroid hormone) deficiency: hypocalcemia, tetany. But the PTH level is normal or elevated.

    Some patients have mutations in the PTH receptor. Others have an abnormal Gs protein that makes inefficient coupling with adenylate cyclase.
  26. Toxic Thyroid Nodules
    These are benign tumors in the thyroid gland that overproduce the hormones.

    Cause: Some patients have an activating somatic mutation in the gene for the TSH receptor. Others have an activating mutation in the Gs protein that keeps it constitutively active, usually by blocking its GTPase activity.
  27. TSH (Thyroid stimulating hormone) from the pituitary gland stimulates
    Hormone production and cell proliferation in the thyroid gland by raising cAMP.
  28. Cholera toxin
    This is an intestinal infection by vibrio cholerae. The bacteria do not invade the tissues, but cause watery diarrhea through a secreted protein toxin.
  29. What happens in cholera toxin
    • The toxin enters the cells, and catalyzes the covalent modification of the α-subunit of the Gs protein. This abolishes the GTPase activity of the Gs protein, leaving it in the active state permanently.
    • cAMP will accumulate
  30. Pertussis toxin
    • Whooping cough:
    • Caused by Bordetella pertussis, which lives on the respiratory epithelium. One of its virulence factors is pertussis toxin.
  31. Pertussis toxin mechanism
    It modifies the α-subunit of the Gi protein. This inactivates the Gi protein.
  32. Resting calcium is always in what portions of the cell
    • Low in the cytoplasm
    • High in ER and mitochondria
  33. What is IP3 and DAG
    Secondary messengers, molecules used in signal transduction and lipid signaling in biological cells. While DAG stays inside the membrane, IP3 is soluble and diffuses through the cell
  34. Elevations of cytoplasmic calcium can be by
    • Hormones acting through a G-protein and IP3
    • A ligand-gated ion channel
    • Voltage-gated calcium channels
  35. Intracellular calcium receptors include:
    • Protein kinase C
    • Calmodulin
    • Troponin C
  36. Muscle contraction is always triggered by calcium, but the mechanisms are different in striated muscle and smooth muscle. What is the difference
    Striated muscle: Calcium binds to troponin C on the thin filaments.

    Smooth muscle: Calcium activates myosin light chain (MLC) kinase.
  37. Membrane-bound guanylate cyclases are activated directly by
  38. Cytoplasmic guanylate cyclase is activated by
    Nitric oxide (NO)
  39. Membrane bound guanylate cyclases are activated directly by, whereas cytoplasmic is activated by
    • Hormones
    • NO
  40. Cyclic GMP synthesis
    GTP - cGMP - GMP (No G-proteins involved)
  41. What is PKA
    Protein Kinase A, it is dependent on cAMP for activation
  42. Calcium contracts vascular smooth muscle triggered by the release of
    • (Nor)epinephrine (α1-receptors)
    • Vasopressin
    • Angiotensin
  43. cAMP relaxes vascular smooth muscle triggered by the release of
    (Nor)epinephrine (β-receptors)
  44. Atial natriuretic factor receptor (ANF)
    A receptor that is ligand activated, activating guanylate cyclase
  45. cGMP relaxes vascular smooth muscle triggered by the release of
    • Nitric oxide
    • Atrial natriuretic factor (ANF)
  46. Nitrovasodilator drugs (nitroglycerin et al.)
    Relax blood vessels because they are metabolized to nitric oxide NO
  47. PDE5 inhibitors (Viagra) inhibit
    A cGMP-specific phosphodiesterase in the corpora cavernosa.
  48. Growth factor receptors mediate
    Mitogenic and/or growth regulatory effects
  49. Growth factor receptors after binding to the growth factor signal do what
    • The receptor autophosphorylates (adds P's)
    • Signaling proteins containing an SH2 domain bind to the autophosphorylated receptor.
    • The signaling proteins become activated allosterically, or tyrosine-phosphorylated by the receptor.Image Upload 6
  50. Insulin receptors are similar to growth factor receptors accept
    The unstimulated receptor is a disulfide-bonded tetramer.

    Most effects are mediated by IRS-1 and IRS-2.
  51. A leprechaun
    Infant born without functional insulin receptors.
  52. After Drinking a cup of coffee you get
    A more active protein kinase A (PKA)
  53. Steroid Hormone receptor is
    A sequence on the DNA that binds to a hormone receptor
  54. Growth factor cascade IP3 system proceeds how
    • 1. Formation of IP3: The autophosphorylated receptor phosphorylates and activates phospholipase C-γ (PLC-γ)
    • 2. PLC converts PIP2 to IP3
    • 3. IP3 triggers calcium release
  55. Activation of protein kinase B growth factors proceeds how
    • 1. Autophosphorylated receptor activates PI3K
    • 2. This produces PIP3 and 3- phosphorylated inositides
    • 3. Insotides activate protein kinase B
  56. The activation of MAP kinases (Growth factor cascade) proceeds how
    • 1. Autophosphorylated receptor activates Ras
    • 2. Ras activates protein kinases
    • 3. Protein kinases phosphorylate and activate MAP kinases
  57. The cascades that are induced by growth factors are out of control in cancer cells. Therefore the best approach for cancer treatment would be a drug that
    Inhibits Akt (Protein kinase B)
  58. PTH causes most of its biological effects by stimulating the production of cAMP, the most likely mutation in a patient who has signs of PTH deficiency (hypocalcemia, Tetany,) but an elevated PTH level is
    A Gs alpha subunit with a reduced affinity for the PTH receptor
  59. The best way to reduce the cAMP level in the intestinal mucosa is by
    Smoke Opium
  60. How do the second messengers DAG and IP3 differ from the cAMP mechanism
    • 1. The GTP Complex cleaves to Phospholipase C
    • 2. Phospholipase C forms DAG and IP3
    • 3. DAG stays in the membrane and activates Protein Kinase C (PKC)
    • 4. IP3 diffuses across the cytoplasm and opens calcium channels in the ER
  61. DAG is short for
  62. PKC is short for
    Protein Kinase C
  63. cAMP is triggered by what hormone in the Liver inducing Glycogen breakdown
  64. cAMP is triggered by what hormone in the Adipose tissue inducing Fat breakdown
    Epinephrine Beta receptors
  65. cAMP is triggered by what hormone in the Bronchial Smooth muscle inducing Relaxation
    Epinephrine beta receptors
  66. cAMP is triggered by what hormone in the vascular smooth muscle inducing Relaxation
    Epinephrine beta receptors
  67. TSH does what to the Thyroid gland
    Triggers Hormone synthesis
  68. ACTH does what to the Adrenal Gland
    Triggers Hormone synthesis
  69. MSH and ACTH does what to the Melanocytes
    Triggers Melanin synthesis
  70. Diarrhea is induced by what hormone in the intestines
    Pancreatic polypeptide
  71. Opiods do what to the brain and Intestines
    Cause constipation in the intestines, and Analgesia (the loss of sense of pain) in the brain
  72. Alpha 2 receptors do what to the brain
    Cause hypotension
  73. Somatostatin has what effect in the pituitary gland
    Inhibition of growth hormone secretion
  74. Melatonin has what effect in the melanocytes
    It inhibits melanin synthesis
  75. The endothelial cells can act as a vasodilator of vascular smooth muscles when triggered by what
    • Acetocholine
    • Bradykinin
    • Histamine
  76. What do endothelial cells release to the smooth muscle causing dilation
    NO which turns GTP to cGMP triggering the response
  77. Epinephrine and Prostacyclin trigger what for relaxation in the vascular smooth muscle
    Conversion of ATP to cAMP
  78. A specific β-adrenergic receptor kinase that phosphorylates only the activated receptor is
    BARK prevents binding of G protein, arrestin follows and degrades it via endocytosis (when degraded, it takes the receptor)
  79. What breaks down cGMP
    PDE-5 (Phosphodiesterase 5)
Card Set
Cell Signaling S1M1