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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
Where are the different **types of** receptors located?
* Type **1+2+3** on the **membrane**. * Type **4** in the **nucleus** and **cytoplasm**.
26
What's the **effector** of a **type 1** receptor?
**Channel.**
27
What's the **effectors** of a **type 2** receptor?
* **Enzyme.** * **Channel.**
28
What's the **effector** of a **type 3** receptor?
**Enzyme.**
29
What's the **effector** of a **type 4** receptor?
Increase or decrease of **gene transcription.**
30
What are the **4** different **signalling paradigms** (patterns)?
* Linear. * Convergent. * Divergent. * Branched.
31
What are the **3** different type of **Ion channel**?
* Voltage-gated. * Ligand-gated. * Mechanically-gated (baroreceptor).
32
What are the main **function** of **ion channels**?
Receptors for fast **neurotransmitters**.
33
What happens when a **agonist binds** to G-protein coupled receptor?
* Alpha **disocciates.** * Receptor **activates**.
34
What is an **agonist**?
**Signalling molecule.**
35
What does the **alpha subunit** of a G-protein do?
Activates the **effector** system.
36
What does the **beta subunit** of a G-protein bind to?
**Phospholipase C**
37
What does the **phospholipase c** **and beta complex** do?
Hydrolyses **PIP2** to **IP3** + **DAG.**
38
How is **calcium released** from the **endoplasmic reticulum** in heterotrimeric G-protein signalling?
IP3 binds to **IP3-gated calcium** receptor.
39
What are the **roles** of the **alpha subunits** within a G-protein?
* Stimulates adenylyl cyclase (cAMP). * Inhibits adenylyl cyclase (cAMP). * Stimulates calcium.
40
What are the **4** main **G-protein** effector systems?
* **Adenylyl cyclase** system. * Calcium release system. * Regulation of **ion channels**. * **Mitogen**-activated protein kinase pathways.
41
What is **GTP**?
**Guanosine triphosphate.**
42
What brakes down **GTP** to **GDP**?
**GTPases.**
43
What is a **mitogen**?
**Signalling molecule** that stimulates **mitosis.**
44
What does **MAPK** stand for?
**Mitogen-activated protein kinases.**
45
Name a receptor that **couples to multiple** G-proteins?
**PAC.**
46
What is **phospholipase c**?
A class of enzymes that **cleave phospholipids** before the phosphate group.
47
What is **cAMP**?
It is a **second messenger** (signalling transducer) derived from **ATP**.
48
What is **adenylyl cyclase**?
Enzyme that converts **ATP** to **cAMP**.
49
What **direction** does the **alpha** sub-unit of a protein control **adenylyl cyclase**?
**Bi-directional.**
50
What does **Heterogeneity** mean?
**Consisting** of **differences**.
51
What does the fact that **G-protein** is **heterogenous** mean?
It can allow different receptors to exert **opposite effects** on a **target enzyme**.
52
What is **cGMP**?
It is a **second messenger** (signalling transducer) derived from **GTP**.
53
What are the functions of **second messengers** (cAMP + cGTP)?
* Activate **protein kinases**. * Activate **cyclic nucleotide-dependant ion channels**. * Activate **enzymes**.
54
What are **cyclic nucleotides**?
A class of molecules that contain a **cyclic bond** and are genereally **second messengers** (signalling transducers).
55
What is **guanylyl cyclase**?
Enzyme that converts **GTP** to **cGMP**.
56
What enzymes are used to control the **cyclic nucleotide levels**?
**Phosphodiesterase enzymes** (PDE's).
57
What do **phosphodiesterases** do?
Catalyse the **hydrolysis** of the **cyclic bond**.
58
What is **ubiquitin**?
**Signalling molecule** that changes the way proteins function - can cause apoptosis in proteins "kiss of death".
59
What does the **ubiquitin-proteasome** **system** do?
**Degrades** misfolded or damaged proteins.
60
What is the ubiquitous **signalling molecule** that **activates calcium** in **gonadotrophs**?
Gonadotropin-releasing hormone
61
What is a **membrane receptor**?
An **integral protein** that **communicates** with the outside of the cell.
62
What is **signal transduction**?
When a ligand **binds** with a receptor causing an **intracellular response**.
63
What are the **2 phases** in GPCR-stimulated **Ca2+ increase**?
* Spike. * Plateau.
64
What causes the Ca2+** spike** phase?
Intracellular Ca2+ mobilisation from **pools in the endoplasmic reticulum**.
65
What causes the Ca2+ **plateau** phase?
Influx via **voltage-operated** **calcium channels****.**
66
What binds to create a **dimer** with **tyrosine-kinase**?
Insulin and growth factor **receptors**.
67
What does the **SH domain protein** do?
Recognises specific phosphotyrosine-containing **regions of tyrosine kinase**.
68
What happens when a **SH domain protein** binds to **tyrozine kinase** **domain** of a tyrozine kinase-linked receptor?
* **Enzyme** activation / **Transcription factor** activation * **Altered gene transcription.** * Tissue response.
69
What are **type 4** receptors?
**Steroid** receptors.
70
What **activates** steroid receptors?
**Ligands.**
71
What's the common **steroid precursor**?
**Cholesterol.**
72
What do **steroids** do?
* **Modify** the transcription of selected genes. * **Bind to promotor** sequences. * **Activate** or **repress transcription**.
73
In a **steroid receptor protein** what are the two terminals?
* **N-terminal** - beginning. * **C-terminal** - end.
74
Where are **steroid receptors** usually found?
**Inside** the cell.
75
What's the importance of the **A/B domain** in steroid hormone receptor?
It is **variable** between receptors.
76
What is the **C domain** of a steroid hormone receptor?
* **Central** domain. * **Cystein** rich. * Contains **finger motifs** that contain zinc - these **bind to DNA**.
77
What is the **D domain** of a steroid hormone receptor?
**Hinge** region - Causes flipping over of receptor (when ligand is bound) allowing it to **bind to DNA in a different way**.
78
What is the **E/F domain** of a steroid hormone receptor?
* Contains **hormone binding** domain. * Contains nuclear **localization signals**. * Contains **transcriptional regulatory** functions * Contains **COOH-terminus**.
79
What happens if their is a **mutation** in the **C domain** of a steroid hormone receptor?
Interuption in **gene transcription** ability.
80
What kind of **steroid** action is **fast**?
**Non-genomic** steroids.
81
What do **kinases** do once **activated**?
* **Translocate** around the cytosol. * **Phosphorylate** target proteins * **Recruit** further kinases.
82
What kind of **signalling molecules** are kinases activated by?
**Primary** signalling molecules or **mitogens**.
83
What is the downstream target of **cAMP**?
**PKA** (protein kinase A)
84
What is a **holoenzyme**?
An **apoenzyme** with a cofactor attached.
85
What is an **apoenzyme**?
An enzyme that needs a **cofactor**.
86
What is a **cofactor**?
A substance whose presence is **essential** for the activity of an enzyme.
87
What **2** parts make up **protein kinase A**?
* 2 **Catalytic** subunits. * 2 **Regulatory** subunits.
88
What does the **catalytic subunit** of **protein kinase A** do?
Adds **phosphate groups** to **proteins**.
89
What does the **regulatory subunit** of **protein kinase A** do?
Mop up excess **cAMP**.
90
What does **MAPK** stand for?
Mitogen-activated protein kinase.
91
What is the **MAPK** pathway?
**Proteins** in the cell that communicate **signal** from a surface **receptor** **to** the **nucleus**.
92
What does the **MAPK** enzymes regulate?
Proliferation.
93
What causes receptor **desensitization**?
Sustained **exposure** to stimuli.
94
What is receptor **desensitization**?
Reduction in **cellular response** over time.
95
What classes of receptors is **desensitization** observed in?
**All** major classes.
96
What is **homologous** desensitization?
Desensitization in response to continued stimulus from an **endogenous** ligand.
97
What is **heterologous** desentsitization?
Desensitization in response to continued stimulus from an other **effector.**
98
What are the **multiple adaptive processes** that take place after a stimulus of the G-protein-coupled receptor?
1. Receptor phosphorylation. 2. **Arrestin** binding. 3. Receptor endocytosis. 4. Endosomal receptor degradion. 5. Receptor transcription inhibited.
99
What is **arrestin**?
A small family of proteins important for **regulating signal transduction** at G protein-coupled receptors.
100
What does **cAMP** do?
* **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).

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