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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

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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
In the intestine, which hormone induces a rise in cyclic AMP ?
Epinephrine
26
In the kidney, which hormone induces a rise in cyclic AMP ?
Vasopressin
27
In the blood platelets, which hormone induces a rise in cyclic AMP ?
Prostaglandin I
28
What is the cellular response to a rise in cyclic AMP in adipose tissue ?
1. Increase in hydrolysis of triglycerides | 2. Decrease in amino acid uptake
29
What is the cellular response to a rise in cyclic AMP in the liver ?
1. Increase in conversion of glycogen to glucose 2. Inhibition of glycogen synthesis 3. Increase in amino acid uptake 4. Increase in glucogenesis
30
What is the cellular response to a rise in cyclic AMP in the ovarian follicle ?
Increase in synthesis of estrogen and prostesterone
31
What is the cellular response to a rise in cyclic AMP in adrenal cortex ?
Increase in the synthesis of aldosterone and cortisol
32
What is the cellular response to a rise in cyclic AMP in the cardiac muscle ?
Increase in contraction rate
33
What is the cellular response to a rise in cyclic AMP in the thyroid gland ?
Secretion of thyroxine
34
What is the cellular response to a rise in cyclic AMP in bone ?
Increase in resorption of calcium from bone
35
What is the cellular response to a rise in cyclic AMP in skeletal muscle ?
Conversion of glycogen to glucose
36
What is the cellular response to a rise in cyclic AMP in intestine ?
Fluid secretion
37
What is the cellular response to a rise in cyclic AMP in kidney ?
Resorption of water ?
38
What is the cellular response to a rise in cyclic AMP in blood platelets ?
Inhibition of aggregation and secretion
39
What are three reasons why so many types of signals can be mediated by a single second messenger (cAMP) ?
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
What are three factors that effect the extracellular signal on different tissues or cell types ?
1. Type of receptor in tissue 2. Type of G protein 3. The set of protein kinase A target proteins in the cell
41
What is the fourth factor which effects why so many types of signals can be mediated by a single second messenger (cAMP)?
The confinement of the signalling process to specific regions within the cell
42
What helps confine a signalling process to specific regions within the cell ?
Adaptor proteins- non catalytic
43
What do adaptor-non catalytic proteins do ?
Hold together signalling proteins in a complex
44
What is an example of a adaptor-non catalytic proteins ?
A kinase anchoring proteins (AKAPs)
45
What are AKAPs ?
Multivalent adaptor proteins
46
How do AKAPs work ?
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
How does a cell achieve integration of signals ?
By summing the influences that lead to an increase or decrease in cyclic AMP
48
What do many G-protein coupled receptors do ?
Activate the phosphoinositide cascade
49
What do second messengers do ?
Relay information from receptor-ligand complex
50
What does the binding of ligands to many cell surface receptors do ?
Increase or decrease in intracellular signaling molecules
51
What does the enzyme phospholipase C do ?
Cleaves PIP2 yielding IP3 and DAG
52
What does IP3 do ?
Increase in cytosolic CA+2
53
What does DAG do ?
Activate protein kinase C
54
What does angiotensin II receptor do ?
Binds peptide hormone involved in controlling blood pressure
55
What is step 1 in the phosphoinositide cascade ?
Ligand binds to g-protein coupled receptor activating the g protein which leads to activation of phospholipase C
56
What is step 2 in the phosphoinositide cascade ?
Phospholipase C cleaves PIP2 yielding IP3 and DAG
57
What is step 3 in the phosphoinositide cascade ?
IP3 diffuses through the cytosol and interacts with and opens CA+2 channels in the endoplasmic reticulum membrane
58
What is step 4 in the phosphoinositide cascade ?
Causing the release of stored Ca+2 ions into the cytosol
59
What is step 5 in the phosphoinositide cascade ?
Rise in cytosolic Ca+2 facilitates recruitment of protein kinase C to membrane
60
What is step 6 in the phosphoinositide cascade ?
Protein kinase C becomes activated by membrane bound DAG
61
What is step 7 in the phosphoinositide cascade ?
Protein kinase C phosphorylates various cellular enzymes and receptors thus altering their activity
62
What is step 8 in the phosphoinositide cascade ?
As the endoplasmic reticulum Ca+2 stores are depleted, Ca+2 channels in plasma membrane open allowing an influx of extracellular Ca+2
63
How is the IP3 initiated signals turned off ?
IP3 is rapidly metabolised to inositol which cannot open the calcium channel
64
How are DAG initiated signals turned off ?
DAG may be phosphorylated to phosphatidate or hydrolysed to glycerol and fatty acids
65
How does calcium work as a second messenger ?
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
What does calcium ion often regulate ?
The regulatory protein calmodulin
67
What does calmodulin act as ?
A calcium sensor in nearly all eukaryotic cells
68
How does calmodulin work ?
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
What family is calmodulin a member of ?
The EF hand protein
70
What is the EF hand formed by ?
Helix-loop-helix unit
71
What else can calmodulin activate ?
Various target proteins such as calmodulin dependent protein kinase
72
What does calmodulin target in calmodulin dependent protein kinase I >
An alpha helix
73
What happens after calcium binding in calmodulin dependent protein kinase I ?
The two sets of EF hands of calmodulin clamp down around the target helix
74
In the pancreas, what hormone induces a rise in calcium ?
Acetylcholine
75
In the parotid salivary gland, what hormone induces a rise in calcium ?
Acetycholine
76
In the vascular or smooth stomach tissue, what hormone induces a rise in calcium ?
Acetylcholine
77
In the liver, what hormone induces a rise in calcium ?
Vasopressin
78
In blood platelets, what hormone induces a rise in calcium ?
Thrombin
79
In mast cells, what hormone induces a rise in calcium ?
Antigen
80
In fibroblasts, what hormone induces a rise in calcium ?
Peptide growth factors
81
What is the cellular response to hormone induced rise in calcium in pancreas ?
Secretion of digestive enzymes such as amylase and trypsinogen
82
What is the cellular response to hormone induced rise in calcium in parotid salivary gland ?
Secretion of amylase
83
What is the cellular response to hormone induced rise in calcium in vascular or stomach smooth muscle ?
Contraction
84
What is the cellular response to hormone induced rise in calcium in the liver ?
Conversion of glycogen to glucose
85
What is the cellular response to hormone induced rise in calcium in blood platelets ?
Aggregation, shape change, secretion of hormones
86
What is the cellular response to hormone induced rise in calcium in mast cells ?
Histamine secretion
87
What is the cellular response to hormone induced rise in calcium in fibroblasts ?
DNA synthesis, cell division

Cells to Organisms - Lectures (36 decks)

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