TLC - L1 - Cell signalling Flashcards

1
Q

What is the receptorome?

A

Part of genome that codes for receptors.

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2
Q

What are the main steps of cell signalling?

A
  • Stimulus.
  • Response.
  • Communication.
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3
Q

What are the 2 types of intercellular signalling?

A
  • Cell surface receptors.
  • Intracellular receptors.
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4
Q

What sort of receptors do hydrophilic signalling molecules attach to?

A

Cell-surface.

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5
Q

What sort of receptors do hydrophobic signalling molecules attach to?

A

Intracellular.

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6
Q

What are the 3 mechanisms of signalling action?

A
  • Autocrine.
  • Paracrine.
  • Endocrine.
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7
Q

What is the autocrine signalling mechanism?

A

Cell responds to stimulus produced by itself.

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8
Q

What is the paracrine signalling mechanism?

A

Cells produces a signal that other cells within same tissue respond to.

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9
Q

What is the endocrine signalling mechanism?

A

Cells produce a signal that is released into blood stream.

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10
Q

What does propagation mean?

A

To transmit.

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11
Q

What kind of signal does a singular signaling cell receive?

A

Weak.

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12
Q

What kind of signal does a cell within a group of identical signaling cells receive?

A

Strong.

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13
Q

How is cell behaviour regulated?

A

Using a combination of signalling molecules (stimuli).

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14
Q

What happens when a cell receives different combinations of signals (stimuli)?

A

Different responses.

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15
Q

The same signalling molecule can produce what kind of responses in different target cells?

A

Different responses.

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16
Q

What responses does acetyl choline provoke in 3 different cell examples?

A
  • Skeletal muscle cell - contraction.
  • Heart muscle cell - relaxation.
  • Secretory cell - secretion.
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17
Q

What is a chemeric receptor?

A

Proteins that allow T-cells to pick out antigens.

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18
Q

What are the 2 different domains of a receptor?

A
  • Ligand-binding (stimulus) domain.
  • Effector domain.
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19
Q

Is it possible to have different signalling molecules that have the same effect?

A

Yes.

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20
Q

What are the major receptor types?

A
  • G-protein coupled receptor.
  • Protein kinase.
  • Ion channel.
  • Transmembrane scaffold.
  • Guanylyl cyclase.
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21
Q

What’s the other name for the G-protein coupled receptor?

A

7-transmembrane domain receptor.

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22
Q

Why do steroids take time to have effect?

A

Because it takes time for them to travel from the nucleus to the plasma membrane.

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23
Q

What is a G-protein?

A

Either heterotrimeric or single subunit with the ability to bind the nucleotides guanosine triphosphate (GTP) and guanosine diphosphate (GDP).

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24
Q

What do G-protein receptors do?

A

Triggered by an external signalling molecule they interact with a G-protein.

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25
Q

Where are the different types of receptors located?

A
  • Type 1+2+3 on the membrane.
  • Type 4 in the nucleus and cytoplasm.
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26
Q

What’s the effector of a type 1 receptor?

A

Channel.

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27
Q

What’s the effectors of a type 2 receptor?

A
  • Enzyme.
  • Channel.
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28
Q

What’s the effector of a type 3 receptor?

A

Enzyme.

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29
Q

What’s the effector of a type 4 receptor?

A

Increase or decrease of gene transcription.

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30
Q

What are the 4 different signalling paradigms (patterns)?

A
  • Linear.
  • Convergent.
  • Divergent.
  • Branched.
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31
Q

What are the 3 different type of Ion channel?

A
  • Voltage-gated.
  • Ligand-gated.
  • Mechanically-gated (baroreceptor).
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32
Q

What are the main function of ion channels?

A

Receptors for fast neurotransmitters.

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33
Q

What happens when a agonist binds to G-protein coupled receptor?

A
  • Alpha disocciates.
  • Receptor activates.
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34
Q

What is an agonist?

A

Signalling molecule.

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35
Q

What does the alpha subunit of a G-protein do?

A

Activates the effector system.

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36
Q

What does the beta subunit of a G-protein bind to?

A

Phospholipase C

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37
Q

What does the phospholipase c and beta complex do?

A

Hydrolyses PIP2 to IP3 + DAG.

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38
Q

How is calcium released from the endoplasmic reticulum in heterotrimeric G-protein signalling?

A

IP3 binds to IP3-gated calcium receptor.

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39
Q

What are the roles of the alpha subunits within a G-protein?

A
  • Stimulates adenylyl cyclase (cAMP).
  • Inhibits adenylyl cyclase (cAMP).
  • Stimulates calcium.
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40
Q

What are the 4 main G-protein effector systems?

A
  • Adenylyl cyclase system.
  • Calcium release system.
  • Regulation of ion channels.
  • Mitogen-activated protein kinase pathways.
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41
Q

What is GTP?

A

Guanosine triphosphate.

42
Q

What brakes down GTP to GDP?

A

GTPases.

43
Q

What is a mitogen?

A

Signalling molecule that stimulates mitosis.

44
Q

What does MAPK stand for?

A

Mitogen-activated protein kinases.

45
Q

Name a receptor that couples to multiple G-proteins?

A

PAC.

46
Q

What is phospholipase c?

A

A class of enzymes that cleave phospholipids before the phosphate group.

47
Q

What is cAMP?

A

It is a second messenger (signalling transducer) derived from ATP.

48
Q

What is adenylyl cyclase?

A

Enzyme that converts ATP to cAMP.

49
Q

What direction does the alpha sub-unit of a protein control adenylyl cyclase?

A

Bi-directional.

50
Q

What does Heterogeneity mean?

A

Consisting of differences.

51
Q

What does the fact that G-protein is heterogenous mean?

A

It can allow different receptors to exert opposite effects on a target enzyme.

52
Q

What is cGMP?

A

It is a second messenger (signalling transducer) derived from GTP.

53
Q

What are the functions of second messengers (cAMP + cGTP)?

A
  • Activate protein kinases.
  • Activate cyclic nucleotide-dependant ion channels.
  • Activate enzymes.
54
Q

What are cyclic nucleotides?

A

A class of molecules that contain a cyclic bond and are genereally second messengers (signalling transducers).

55
Q

What is guanylyl cyclase?

A

Enzyme that converts GTP to cGMP.

56
Q

What enzymes are used to control the cyclic nucleotide levels?

A

Phosphodiesterase enzymes (PDE’s).

57
Q

What do phosphodiesterases do?

A

Catalyse the hydrolysis of the cyclic bond.

58
Q

What is ubiquitin?

A

Signalling molecule that changes the way proteins function - can cause apoptosis in proteins “kiss of death”.

59
Q

What does the ubiquitin-proteasome system do?

A

Degrades misfolded or damaged proteins.

60
Q

What is the ubiquitous signalling molecule that activates calcium in gonadotrophs?

A

Gonadotropin-releasing hormone

61
Q

What is a membrane receptor?

A

An integral protein that communicates with the outside of the cell.

62
Q

What is signal transduction?

A

When a ligand binds with a receptor causing an intracellular response.

63
Q

What are the 2 phases in GPCR-stimulated Ca2+ increase?

A
  • Spike.
  • Plateau.
64
Q

What causes the Ca2+ spike phase?

A

Intracellular Ca2+ mobilisation from pools in the endoplasmic reticulum.

65
Q

What causes the Ca2+ plateau phase?

A

Influx via voltage-operated calcium channels.

66
Q

What binds to create a dimer with tyrosine-kinase?

A

Insulin and growth factor receptors.

67
Q

What does the SH domain protein do?

A

Recognises specific phosphotyrosine-containing regions of tyrosine kinase.

68
Q

What happens when a SH domain protein binds to tyrozine kinase domain of a tyrozine kinase-linked receptor?

A
  • Enzyme activation / Transcription factor activation
  • Altered gene transcription.
  • Tissue response.
69
Q

What are type 4 receptors?

A

Steroid receptors.

70
Q

What activates steroid receptors?

A

Ligands.

71
Q

What’s the common steroid precursor?

A

Cholesterol.

72
Q

What do steroids do?

A
  • Modify the transcription of selected genes.
  • Bind to promotor sequences.
  • Activate or repress transcription.
73
Q

In a steroid receptor protein what are the two terminals?

A
  • N-terminal - beginning.
  • C-terminal - end.
74
Q

Where are steroid receptors usually found?

A

Inside the cell.

75
Q

What’s the importance of the A/B domain in steroid hormone receptor?

A

It is variable between receptors.

76
Q

What is the C domain of a steroid hormone receptor?

A
  • Central domain.
  • Cystein rich.
  • Contains finger motifs that contain zinc - these bind to DNA.
77
Q

What is the D domain of a steroid hormone receptor?

A

Hinge region - Causes flipping over of receptor (when ligand is bound) allowing it to bind to DNA in a different way.

78
Q

What is the E/F domain of a steroid hormone receptor?

A
  • Contains hormone binding domain.
  • Contains nuclear localization signals.
  • Contains transcriptional regulatory functions
  • Contains COOH-terminus.
79
Q

What happens if their is a mutation in the C domain of a steroid hormone receptor?

A

Interuption in gene transcription ability.

80
Q

What kind of steroid action is fast?

A

Non-genomic steroids.

81
Q

What do kinases do once activated?

A
  • Translocate around the cytosol.
  • Phosphorylate target proteins
  • Recruit further kinases.
82
Q

What kind of signalling molecules are kinases activated by?

A

Primary signalling molecules or mitogens.

83
Q

What is the downstream target of cAMP?

A

PKA (protein kinase A)

84
Q

What is a holoenzyme?

A

An apoenzyme with a cofactor attached.

85
Q

What is an apoenzyme?

A

An enzyme that needs a cofactor.

86
Q

What is a cofactor?

A

A substance whose presence is essential for the activity of an enzyme.

87
Q

What 2 parts make up protein kinase A?

A
  • 2 Catalytic subunits.
  • 2 Regulatory subunits.
88
Q

What does the catalytic subunit of protein kinase A do?

A

Adds phosphate groups to proteins.

89
Q

What does the regulatory subunit of protein kinase A do?

A

Mop up excess cAMP.

90
Q

What does MAPK stand for?

A

Mitogen-activated protein kinase.

91
Q

What is the MAPK pathway?

A

Proteins in the cell that communicate signal from a surface receptor to the nucleus.

92
Q

What does the MAPK enzymes regulate?

A

Proliferation.

93
Q

What causes receptor desensitization?

A

Sustained exposure to stimuli.

94
Q

What is receptor desensitization?

A

Reduction in cellular response over time.

95
Q

What classes of receptors is desensitization observed in?

A

All major classes.

96
Q

What is homologous desensitization?

A

Desensitization in response to continued stimulus from an endogenous ligand.

97
Q

What is heterologous desentsitization?

A

Desensitization in response to continued stimulus from an other effector.

98
Q

What are the multiple adaptive processes that take place after a stimulus of the G-protein-coupled receptor?

A
  1. Receptor phosphorylation.
  2. Arrestin binding.
  3. Receptor endocytosis.
  4. Endosomal receptor degradion.
  5. Receptor transcription inhibited.
99
Q

What is arrestin?

A

A small family of proteins important for regulating signal transduction at G protein-coupled receptors.

100
Q

What does cAMP do?

A
  • Transfers the effects of hormones like glucagon and adrenaline, which cannot pass through the plasma membrane.
  • Activation of protein kinases - regulates the effects of adrenaline and glucagon.
  • Regulates ion channels (such as the HCN channels).