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Biology of the Cell > Unit 2: Cell signalling (Lectures 1-4) > Flashcards

Unit 2: Cell signalling (Lectures 1-4) Flashcards

1
Q

What are the 5 types of extracellular signalling molecule ?

A

1) Contact dependant
2) Autocrine
3) Paracrine
4) Synaptic
5) Endocrine

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2
Q

What are the 2 types of receptor proteins ?

A

1) Cell surface receptors
2) Intracellular receptors

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3
Q

What is specificity ?

A

Where receptors only recognise and bind to specific ligands

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4
Q

What is a ligand ?

A

A molecule that can bind to a receptor

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5
Q

What is an agonist ?

A

Ligands that bind to receptors and produce a biological response

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6
Q

What is an antagonist ?

A

Ligands that bind to receptors but do not produce a biological response. When antagonists bind to a receptor they prevent agonists from binding

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7
Q

What are the features of a receptor (2)?

A
  • Ligand binding domain
  • Effector domain
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8
Q

What is an effector domain ?

A

The domain that determines the downstream biological processes that occur following the ligand binding

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9
Q

What are the 4 main types of intercellular signalling ?

A

1) Ion channels
2) G protein coupled receptors
3) Enzyme coupled receptors
4) Nuclear receptors

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10
Q

What is a molecular switch ?

A

Proteins that activate or deactivate their target proteins

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11
Q

What is a signalling cascade ?

A

A series of activation or inhibition steps

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12
Q

What do protein kinases do ?

A

Add phosphate groups

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13
Q

What do protein phosphates do ?

A

Remove phosphate groups

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14
Q

What does GDP stand for ?

A

Guanosine Diphosphate

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15
Q

What are the 4 different types of signalling pathways ?

A

1) Linear/ Parallel
2) Convergent
3) Divergent
4) Multiply branched

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16
Q

Explain a linear/parallel pathway

A

1 receptor goes to 1 transducer that goes to 1 effector

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17
Q

Explain a convergent signalling pathway

A

3 receptors go to 2 transducers that go to 1 effector

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18
Q

Explain a divergent signalling pathway

A

1 receptor goes to 2 transducers that goes to 3 effectors

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19
Q

Describe a multiply branched signalling pathway

A

Multiple receptors go to multiple transducers that goes to multiple effectors

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20
Q

What causes receptor desensitisation ?

A

Sustained/ Prolonged exposure to stimuli

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21
Q

What are the 4 different types of ion channels ?

A

1) Voltage gated
2) Ligand gated (Extracellular ligand)
3) Ligand gated (Intracellular ligand)
4) Mechanically gated

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22
Q

What is homologous desensitisation ?

A

It is in response to continuous stimulus from endogenous ligand for a receptor

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23
Q

What is heterologous desensitisation ?

A

It is in response to continuous stimulus from another effector

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24
Q

What are the 2 types of receptor desensitisation ?

A
  • Homologous
  • Heterologous
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25
Do ion channels show ion selectivity ?
Yes they do
26
How do ligand gated ion channels change from an inactive to active receptor state ?
With an agonist binding
27
How do ligand gated ion channels change from an active receptor to a desensitised receptor ?
With the continuous application of an agonist
28
How do ligand ion channels change from a desensitised receptor to an inactive receptor ?
Agonist withdrawal
29
What are GPCRs ?
G proteins coupled receptors
30
What is the structure of a GPCR ?
- Single polypeptide chain - 7 transmembrane domains - Ligand binding domain
31
How are GPCRs activated ?
1) The binding of an extracellular ligand changes the conformation of a receptor 2) This activates the G protein
32
Explain the cAMP pathway (4)
1) Gas subunit is activated by GPCR 2) This activates adenylyl cyclase and produces cAMP 3) cAMP targets protein kinase A 4) Binding of cAMP to PKA releases catalytic subunits meaning they are able to phosphorylate their targets
33
Explain the IP3 pathway (7)
1) Gaq subunit is activated by GPCR 2) This activates phospholipase C 3) Phospholipase C is an enzyme that hydrolyses PI(4,5)P2 to generate IP3 and diacylglycerol 4) IP3 releases calcium from ER stores 5) Diacylglycerol and calcium activate protein kinase C 6) Protein kinase C phosphorylates target proteins 7) Calcium acts as mediator
34
What does calcium trigger in cardiomyocytes ?
Contraction of cardiomyocytes (As cytoplasmic calcium increases)
35
What is the most common type of enzyme coupled receptor ?
Receptor tyrosine kinases (RTKs)
36
Explain the MAPK pathway (6)
1) Ligand binding causes the receptor to dimerise 2) Dimerisation leads to receptor activation (Thyrosine autophosphorylation) 3) Phosphorylated sites on RTKs act as doing sites for adaptor proteins with SH2 domains 4) Adaptor proteins activate Ras, a monomeric GTPase 5) Ras activates a kinase cascade, that involves mitogen activated protein kinases (MAPK) 6) This phosphorylates transcription factors to regulate cell proliferation
37
What is VEGF ?
A family of proteins that's expression is regulated by hypoxia
38
What is VEGF secreted by ?
Tumor cells- driven by oncogenes such as Ras and Raf
39
What is angiogenesis ?
The formation of new capillaries from existing blood vessels
40
How does angiogenesis occur ?
By the proliferation and movement of endothelial cells
41
How does VEGF direct angiogenesis (5) ?
1) Endothelial cells exposed to VEGF become tip cells 2) Tip cells lead the developing sprout by extending filopodia 3) The developing sprout elongates until a lumen is created 4) Blood flow through the new capillary is established 5) The new capillary is stabilised by pericytes
42
What is a trigger of angiogenesis ?
Hypoxia
43
What is hypoxia ?
A deficiency of oxygen in the tissues
44
What is HIF-1a ?
A transcription that increases the transcription of pro-angiogenic genes such as VEGF
45
What are 5 biological roles of VEGF ?
1) Important in vasculogenesis 2) Regulates body growth and development 3) Regulates kidney function 4) Required for bone formation and longitudinal bone growth 5) Angiogenesis in the ovarian cycle
46
When is there too much VEGF ?
- VEGF is secreted by many solid tumours - Suggests role of VEGF in angiogenesis of tumours: allows growth to occur
47
What can be used to inhibit VEGF action ?
Anti- VEGF monoclonal antibodies such as bevacizumab - Reduces tumour spreading
48
What diseases can it lead to if too little VEGF ?
- Spinal chord perfusion - Nervous degeneration
49
What is the link between VEGF and neurodegenerative diseases ?
Too little VEGF= Not enough neuro protection Too much VEGF = BBB breakdown and vascular leakage
50
What is BBB ?
The blood brain barrier
51
What is the main function of nuclear receptors ?
To regulate gene transcription: ligand activated transcription factors
52
What are the 4 main components of nuclear receptor structure ?
1) N-terminal domain 2) DNA binding domain 3) Hinge region 4) Ligand binding domain
53
What are the 4 classes of nuclear receptor mechanisms of action ?
1) Steroid receptors 2) Retinoid X Receptor heterodimers 3) Dimeric orphan receptors 4) Monomeric orphan receptors
54
What type of hormone are oestrogens ?
Steroid hormones that are derived from cholesterol
55
How is oestrogen biosynthesised ?
Cholesterol to Progestins to Androgens to Oestrogens
56
What is the job of CYP19 ?
It encodes aromatase cytochrome P450 which is involved in oestrogen biosynthesis
57
What is the job of nuclear receptors Era and Erb ?
They are oestrogen receptors that bind oestrogens with a high affinity
58
Is oestrogen hydrophobic or hydrophilic and what does this mean ?
It is hydrophobic and can pass through the cell membrane
59
Explain the mechanism of thyroid hormone action (4)
1) Thyroid hormones enter the cell via thyroid hormone transporters 2) They are metabolised by deiodinase enzymes 3) The hormone T3 binds to the thyroid hormone receptor (TR) which is in the nucleus 4) T3 binding to TR leads to the dissociation of corepressors and their replacement with coactivator complexes promoting transcription of thyroid hormone responsive genes
60
What is hypothyroidism ?
The under secretion of thyroid hormone
61
What is hyperthyroidism ?
The over secretion of thyroid hormone
62
What is the treatment for hypothyroidism ?
Replacement with oral T4
63
What are some treatments for hyperthyroidism ?
- Medication to reduce thyroid hormone production - Surgical removal of thyroid gland - Treatment with radioactive iodine

Biology of the Cell (10 decks)

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