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Cells to Organisms - Lectures > Lecture 13. Signalling Through G-Protein Coupled Receptors > Flashcards

Lecture 13. Signalling Through G-Protein Coupled Receptors Flashcards

1
Q

When does the B-Adrenergic receptor signalling pathway become activated ?

A

When the body is under stress

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2
Q

What can a single hormone receptor complex stimulate ?

A

Nucleotide exchange in many G-protein heterotrimers

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3
Q

What is step 1. in the B-Adrenergic signalling pathway ?

A

Epinephrine binds to the receptor resulting in an activated receptor

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4
Q

What is step 2. in the B-Adrenergic signalling pathway ?

A

GTP is exchanged for GDP resulting in amplification and an activated G protein

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5
Q

What is step 3. in the B-Adrenergic signalling pathway ?

A

There is a protein-protein interaction resulting in amplification and an activated adenylate cyclase

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6
Q

What is step 4. in the B-Adrenergic signalling pathway ?

A

An enzymatic reaction occurs resulting in amplification and increased cyclic AMP

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7
Q

What is step 5. in B-Adrenergic signalling pathway ?

A

The increased cyclic AMP activates protein kinase A and other effector enzymes

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8
Q

What is step 6. in B-Adrenergic signalling pathway ?

A

Each protein kinase A phosphorylates hundreds of proteins

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9
Q

How is the B-Adrenergic signalling pathway terminated ?

A

G-proteins spontaneously hydrolyse GTP to GDP thus resetting themselves

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10
Q

What ability do G-proteins have ?

A

Intrinsic GTPase activity

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11
Q

How is the signal transduction by the G-protein coupled receptor terminated in B-Adrenergic pathway ?

A
  1. Dissociation of signalling molecules from receptor

2. Phosphorylation of cytoplasmic C-terminus of receptors and subsequent binding of B-arrestin

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12
Q

What is the function of B-arrestin?

A

Desensitisation

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13
Q

Under stress all tissues have an increased need for ??

A

Fuels like glucose (glycogenolysis) and fatty acids (lipolysis)

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14
Q

Where do liberated glucose and fatty acids as a result of epinephrine/adrenaline bind to ?

A

Hepatic and adipose cells respectively

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15
Q

Where else can epinephrine bind to ?

A

B-Adrenergenic receptors on heart

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16
Q

What do B-Adrenergic receptors on the heart do ?

A

Increase the heart contraction rate which increases blood supply to the heart

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17
Q

In the adipose tissue, which hormone induces a rise in cyclic AMP ?

A
  1. Epinephrine
  2. ACTH
  3. Glucagon
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18
Q

In the liver, which hormone induces a rise in cyclic AMP ?

A
  1. Epinephrine
  2. Norepinephrine
  3. Glucagon
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19
Q

In the ovarian follicle, which hormone induces a rise in cyclic AMP ?

A
  1. FSH

2. LH

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20
Q

In the adrenal cortex, which hormone induces a rise in cyclic AMP ?

A

ACTH

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21
Q

In the cardiac muscle, which hormone induces a rise in cyclic AMP ?

A

Epinephrine

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22
Q

In the thyroid gland, which hormone induces a rise in cyclic AMP ?

A

TSH

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23
Q

In the bone, which hormone induces a rise in cyclic AMP ?

A

Parathyroid Hormone

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24
Q

In the skeletal muscle, which hormone induces a rise in cyclic AMP ?

A

Epinephrine

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25
Q

In the intestine, which hormone induces a rise in cyclic AMP ?

A

Epinephrine

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26
Q

In the kidney, which hormone induces a rise in cyclic AMP ?

A

Vasopressin

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27
Q

In the blood platelets, which hormone induces a rise in cyclic AMP ?

A

Prostaglandin I

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28
Q

What is the cellular response to a rise in cyclic AMP in adipose tissue ?

A
  1. Increase in hydrolysis of triglycerides

2. Decrease in amino acid uptake

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29
Q

What is the cellular response to a rise in cyclic AMP in the liver ?

A
  1. Increase in conversion of glycogen to glucose
  2. Inhibition of glycogen synthesis
  3. Increase in amino acid uptake
  4. Increase in glucogenesis
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30
Q

What is the cellular response to a rise in cyclic AMP in the ovarian follicle ?

A

Increase in synthesis of estrogen and prostesterone

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31
Q

What is the cellular response to a rise in cyclic AMP in adrenal cortex ?

A

Increase in the synthesis of aldosterone and cortisol

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32
Q

What is the cellular response to a rise in cyclic AMP in the cardiac muscle ?

A

Increase in contraction rate

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33
Q

What is the cellular response to a rise in cyclic AMP in the thyroid gland ?

A

Secretion of thyroxine

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34
Q

What is the cellular response to a rise in cyclic AMP in bone ?

A

Increase in resorption of calcium from bone

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35
Q

What is the cellular response to a rise in cyclic AMP in skeletal muscle ?

A

Conversion of glycogen to glucose

36
Q

What is the cellular response to a rise in cyclic AMP in intestine ?

A

Fluid secretion

37
Q

What is the cellular response to a rise in cyclic AMP in kidney ?

A

Resorption of water ?

38
Q

What is the cellular response to a rise in cyclic AMP in blood platelets ?

A

Inhibition of aggregation and secretion

39
Q

What are three reasons why so many types of signals can be mediated by a single second messenger (cAMP) ?

A
  1. Some hormones act by inhibiting adenylate cyclase, lowering cyclic AMP and suppressing phosphorylation by protein kinase A.
  2. Prostaglandin E1 stimulated cyclic AMP synthesis because its receptors are coupled to stimulatory Gs
  3. An extracellular signal can have very different effects on different tissues or cell types
40
Q

What are three factors that effect the extracellular signal on different tissues or cell types ?

A
  1. Type of receptor in tissue
  2. Type of G protein
  3. The set of protein kinase A target proteins in the cell
41
Q

What is the fourth factor which effects why so many types of signals can be mediated by a single second messenger (cAMP)?

A

The confinement of the signalling process to specific regions within the cell

42
Q

What helps confine a signalling process to specific regions within the cell ?

A

Adaptor proteins- non catalytic

43
Q

What do adaptor-non catalytic proteins do ?

A

Hold together signalling proteins in a complex

44
Q

What is an example of a adaptor-non catalytic proteins ?

A

A kinase anchoring proteins (AKAPs)

45
Q

What are AKAPs ?

A

Multivalent adaptor proteins

46
Q

How do AKAPs work ?

A

One part binds to R subunits of protein kinase A and another to the specific structure within the cell that confines protein kinase A to the vicinity of tjat structure

47
Q

How does a cell achieve integration of signals ?

A

By summing the influences that lead to an increase or decrease in cyclic AMP

48
Q

What do many G-protein coupled receptors do ?

A

Activate the phosphoinositide cascade

49
Q

What do second messengers do ?

A

Relay information from receptor-ligand complex

50
Q

What does the binding of ligands to many cell surface receptors do ?

A

Increase or decrease in intracellular signaling molecules

51
Q

What does the enzyme phospholipase C do ?

A

Cleaves PIP2 yielding IP3 and DAG

52
Q

What does IP3 do ?

A

Increase in cytosolic CA+2

53
Q

What does DAG do ?

A

Activate protein kinase C

54
Q

What does angiotensin II receptor do ?

A

Binds peptide hormone involved in controlling blood pressure

55
Q

What is step 1 in the phosphoinositide cascade ?

A

Ligand binds to g-protein coupled receptor activating the g protein which leads to activation of phospholipase C

56
Q

What is step 2 in the phosphoinositide cascade ?

A

Phospholipase C cleaves PIP2 yielding IP3 and DAG

57
Q

What is step 3 in the phosphoinositide cascade ?

A

IP3 diffuses through the cytosol and interacts with and opens CA+2 channels in the endoplasmic reticulum membrane

58
Q

What is step 4 in the phosphoinositide cascade ?

A

Causing the release of stored Ca+2 ions into the cytosol

59
Q

What is step 5 in the phosphoinositide cascade ?

A

Rise in cytosolic Ca+2 facilitates recruitment of protein kinase C to membrane

60
Q

What is step 6 in the phosphoinositide cascade ?

A

Protein kinase C becomes activated by membrane bound DAG

61
Q

What is step 7 in the phosphoinositide cascade ?

A

Protein kinase C phosphorylates various cellular enzymes and receptors thus altering their activity

62
Q

What is step 8 in the phosphoinositide cascade ?

A

As the endoplasmic reticulum Ca+2 stores are depleted, Ca+2 channels in plasma membrane open allowing an influx of extracellular Ca+2

63
Q

How is the IP3 initiated signals turned off ?

A

IP3 is rapidly metabolised to inositol which cannot open the calcium channel

64
Q

How are DAG initiated signals turned off ?

A

DAG may be phosphorylated to phosphatidate or hydrolysed to glycerol and fatty acids

65
Q

How does calcium work as a second messenger ?

A

Calcium binds tightly to proteins and induces conformational changes.

Calcium ions bind tightly to negatively charged oxygen atoms (6-8) which enables it to cross link different segment of proteins inducing conformational changes

66
Q

What does calcium ion often regulate ?

A

The regulatory protein calmodulin

67
Q

What does calmodulin act as ?

A

A calcium sensor in nearly all eukaryotic cells

68
Q

How does calmodulin work ?

A
  1. When cytosolic Ca+2 level is raised above 500nM, calmodulin is activated by Ca+2 binding.
  2. It then undergoes a conformational change which exposes hydrophobic surfaces which bind to other places.
69
Q

What family is calmodulin a member of ?

A

The EF hand protein

70
Q

What is the EF hand formed by ?

A

Helix-loop-helix unit

71
Q

What else can calmodulin activate ?

A

Various target proteins such as calmodulin dependent protein kinase

72
Q

What does calmodulin target in calmodulin dependent protein kinase I >

A

An alpha helix

73
Q

What happens after calcium binding in calmodulin dependent protein kinase I ?

A

The two sets of EF hands of calmodulin clamp down around the target helix

74
Q

In the pancreas, what hormone induces a rise in calcium ?

A

Acetylcholine

75
Q

In the parotid salivary gland, what hormone induces a rise in calcium ?

A

Acetycholine

76
Q

In the vascular or smooth stomach tissue, what hormone induces a rise in calcium ?

A

Acetylcholine

77
Q

In the liver, what hormone induces a rise in calcium ?

A

Vasopressin

78
Q

In blood platelets, what hormone induces a rise in calcium ?

A

Thrombin

79
Q

In mast cells, what hormone induces a rise in calcium ?

A

Antigen

80
Q

In fibroblasts, what hormone induces a rise in calcium ?

A

Peptide growth factors

81
Q

What is the cellular response to hormone induced rise in calcium in pancreas ?

A

Secretion of digestive enzymes such as amylase and trypsinogen

82
Q

What is the cellular response to hormone induced rise in calcium in parotid salivary gland ?

A

Secretion of amylase

83
Q

What is the cellular response to hormone induced rise in calcium in vascular or stomach smooth muscle ?

A

Contraction

84
Q

What is the cellular response to hormone induced rise in calcium in the liver ?

A

Conversion of glycogen to glucose

85
Q

What is the cellular response to hormone induced rise in calcium in blood platelets ?

A

Aggregation, shape change, secretion of hormones

86
Q

What is the cellular response to hormone induced rise in calcium in mast cells ?

A

Histamine secretion

87
Q

What is the cellular response to hormone induced rise in calcium in fibroblasts ?

A

DNA synthesis, cell division

Cells to Organisms - Lectures (36 decks)

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