Lecture 12. Intracellular Signal Transduction: Conserved Mechanisms for Responding to Extracellular Signals Flashcards

1
Q

What are the seven steps involved in communication by extracellular signals ?

A
  1. Synthesis
  2. Release of signalling molecule by signalling cell
  3. Transport of signal to target cell
  4. Detection of signal by specific receptor proteins
  5. Transduction of signal
  6. Response
  7. Termination of signal
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2
Q

What are the general signalling schemes ?

A
  1. Endocrine signalling
  2. Paracrine signalling
  3. Autocrine signalling
  4. Signalling by plasma membrane attached proteins
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3
Q

What are the cell surface receptors ?

A
  1. G protein coupled receptors
  2. Ion channel receptors
  3. Tyrosine kinase linked receptors
  4. Receptors with intrinsic enzymatic activity
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4
Q

How do G protein coupled receptors work ?

A
  1. Ligand binding activates a GTP binding protein.
  2. This G protein then either activates or inhibits an enzyme that generates a specific second messenger or modulates an ion channel causing a change in membrane potential.
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5
Q

How do ion channel receptors work ?

A

Ligand binding changes the receptor confirmation such that a specific ion channel is opened

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6
Q

How do tyrosine kinase-linked receptors work ?

A

Ligand binding stimulates formation of a dimeric receptor which interacts and activates cytosolic protein tyrosine kinase

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7
Q

How do receptors with intrinsic enzymatic activity work ?

A

Ligand binding changes receptor confirmation and activates catalytic activity

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8
Q

What is an example of a G protein coupled receptor ?

A

Epinephrine

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9
Q

What is an example of ion channel receptors ?

A

Acetylcholine

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10
Q

What is an example of tyrosine kinase linked receptors ?

A

Erythropoietin

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11
Q

What is an example of receptors with intrinsic enzymatic activity ?

A

Insulin

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12
Q

How do you classify hormones based on their solubility and receptor location ?

A
  1. Lipophilic hormones with intracellular receptors
  2. Lipophilic hormones with cell-surface receptors
  3. Hydrophilic hormones with cell surface receptors
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13
Q

What are some example of lipophilic hormones with intracellular receptors ?

A
  1. Steroid hormones
  2. Thyroxine
  3. Vitamin D
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14
Q

What is an example of a lipophilic hormone with cell surface receptors ?

A

Prostaglandins

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15
Q

What are the two classes of hydrophilic hormones with cell surface receptors and give examples ?

A
  1. Peptide hormones for example insulin and glucagon

2. Small charged molecules for example epinephrine and histamine

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16
Q

What are some examples of signal transduction pathways ?

A
  1. Epinephrine and B-Adrenergic receptor
  2. Insulin and insulin receptor
  3. Epidermal growth factor (EGF) and EGF receptor
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17
Q

What does the epinephrine and B-Adrenergic receptor signal transduction pathway do ?

A

Energy store mobilisation

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18
Q

What does the insulin and insulin receptor signal transduction pathway do ?

A

Increase glucose uptake

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19
Q

What does EGF and EGFF receptor signal transduction pathway do ?

A

Expression of growth promoting genes

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20
Q

What do second messengers do ?

A

Relay information from receptor-ligand complex

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21
Q

What does binding of ligand to many cell surface receptors lead to ?

A

Increase or decrease in intracellular signalling molecules ie. second messengers

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22
Q

What are some common second messengers ?

A
  1. cAMP, cGMP
  2. Calcium ion
  3. Inositol 1,4,5-triphosphate (IP3)
  4. Diacylglycerol (DAG)
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23
Q

What are second messengers often free to do ?

A

Diffuse to other compartments of cell for example the nucleus influencing gene expression

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24
Q

What may be amplified in generation of second messengers ?

A

Signal

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25
Q

What does the use of common second messengers in multiple signalling pathways create ?

A

Opportunities (cross talk) and potential problems

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26
Q

What is a common means of information transfer ?

A

Protein phosphorylation

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27
Q

How are proteins phosphorylated ?

A

Specific enzymes known as protein kinases phosphorylate target proteins

28
Q

What is the most common donor of phosphate groups ?

A

ATP

29
Q

How does a protein kinase phosphorylate ?

A

Protein kinases transfer phosphoryl groups from ATP to specific serine, threonine and tyrosine residues on specific proteins

30
Q

What do protein phosphatases do ?

A

Catalyse the hydrolytic removal of phosphate groups

31
Q

What are phosphorylation and dephosphorylation reaction not ?

A

They are not the reverse of one another. They are essentially irreversible under physiological conditions

32
Q

Where will phosphorylation of a specific substrate only take place ?

A

In the presence of a specific protein kinase

33
Q

Where will the dephosphorylation of a specific substrate only take place ?

A

In the presence of a specific phosphatase

34
Q

How do protein kinases and phosphatases work together ?

A

They work independently and in balance to regulate the function of proteins

35
Q

What type of strategy of phosphorylation ?

A

A valuable regulatory strategy

36
Q

What way is the free energy of phosphorylation ?

A

Very large

37
Q

What does the large free energy of phosphorylation do ?

A

Changes the conformational equilibrium between different functional states of the function

38
Q

What is the most common cellular energy currency ?

A

ATP

39
Q

What does the use of ATP as the phosphoryl donor group link ?

A

The energy status of the cell to regulation of metabolism

40
Q

What does addition of a phosphate group to the protein do ?

A

Adds two negative charges to the protein allowing new electrostatic interactions to be formed

41
Q

What can a phosphate group form ?

A

Three or more hydrogen bonds

42
Q

What does the formation of three or more hydrogen bonds allow ?

A

Specific interactions with other hydrogen bond donors

43
Q

What is the time frame for phosphorylation and dephosphorylation ?

A

Can take place within a second and up to hours

44
Q

What does phosphorylation often result in ?

A

Highly amplified effects

45
Q

What amplification mean ?

A

When enzymes activate enzymes, the number of affected molecules increases geometrically in an enzyme cascade

46
Q

What does cyclic AMP activate ?

A

Protein kinase A

47
Q

How does cyclic AMP activate protein kinase A ?

A

By altering the quaternary structure

48
Q

What is the structure of protein kinase A ?

A

Tetramer containing two regulatory R subunits and two catalytic C subunits

49
Q

What is the other name for the PKA tetramer ?

A

R2C2

50
Q

What happens in the absence of cyclic AMP ?

A

R2C2 is catalytically inactive

51
Q

What are G protein coupled receptors responsible for ?

A

Relaying information from many diverse signals for example photons, hormones, neurotransmitters

52
Q

What is the structure of G protein coupled receptors ?

A

Contain seven helices that span the membrane bilayer: seven transmembrane helix (7TM) receptors

53
Q

What in the G protein coupled receptor changes confirmation in response to ligand binding ?

A

They cytoplasmic loops and C-termini

54
Q

What does the conformational changes in the cytoplasmic loops and c-termini result in ?

A

The activation of G-proteins

55
Q

What are some of the biological functions mediated by G-protein coupled receptors or 7TM receptors ?

A
  1. Smell
  2. Taste
  3. Neurotransmission
  4. Hormone action
  5. Hormone secretion
  6. Control of blood pressure
  7. Embryogenesis
  8. Development
  9. Vision
  10. Viral infection
56
Q

What does rhodopsin take part in ?

A

Visual signal transduction

57
Q

Where is the ligand binding site of of G-protein coupled receptors rhodopsin ?

A

Near the extracellular surface

58
Q

What is the importance of G-protein coupled receptors ?

A
  1. Involvement in many diseases
  2. Target of almost half of all modern pharmaceutical drugs
    3.
59
Q

In heterotrimeric G-proteins what does the alpha subunit bind ?

A

Nucleotide

60
Q

What is the structure of the beta subunit in the heterotrimeric G-protein ?

A

Seven bladed propeller structure

61
Q

What is the structure of the gamma subunit in the heterotrimeric G-protein ?

A

Pair of alpha helices that wrap around the beta subunit

62
Q

Where are the alpha and gamma subunit of the heterotrimeric G-protein usually anchored to and by what ?

A

The membrane by covalently attached fatty acids

63
Q

What happens to the alpha subunit once GTP binds to it ?

A

It changes conformation and dissociates from the beta- gamma dimer

64
Q

How do activated G proteins transmit signals ?

A

By binding to other proteins, often enzymes

65
Q

What do GDP and GTP act as ?

A

on/off molecular switches

66
Q

What are the important classes of molecules involved in signal transduction pathways ?

A
  1. Signalling molecules
  2. Receptors
  3. G proteins
  4. Effector enzymes
  5. Second messengers
  6. Protein kinases
  7. Phosphatases
67
Q

What is an example of an effector enzyme ?

A

Adenylate cyclase