Receptor Mechanism Flashcards by Carys Hooper

What does acetylcholine do in the salivary gland?

Secretion

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What does acetylcholine do in the heart muscle?

Decreased rate and force of contraction

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What does acetylcholine do in the skeletal muscle?

Contraction

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What model do receptors work under?

Lock and key model

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What’s the fastest receptor?

Ligand gated ion channel

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What’s the slowest receptor?

Nuclear

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Give examples of ligand gated ion channel agonists

nicotinic cholinoceptor 5HT3
acetylcholine 5HT
gamma amino butyrate acid (gaba) glycine

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How many similar proteins does a ligand gated ion receptor have?

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Where is the amino acid terminus in a ligand gated ion channel?

External

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How many transmembrane domains do ligand gated ion channels have?

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Which amino acids form domains and which form the chains between domains?

Hydrophobic amino acids form domains

Hydrophilic amino acids form the Chains

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How many transmembrane domains do nicotinic acetylcholine have per protein?

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What is the nicomic acetylcholine made up of?

2 alpha subunits
1 beta subunit
1 gamma subunit
1 delta subunit

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How do the agonists activate the ligand gated ion channel?

Bind to the alpha subunits which causes a molecular kink

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How do nicotinic and 5HT3 depolarise?

Na/Ca influx

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How does GABAa and glycine hyperpolarise?

Chloride influx

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What is the nicotinic acetylcholine receptor made up of in adult skeletal muscle?

Alpha 1 
Epsilon
Alpha 1
Beta 1
Delta

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What is the nicotinic acetylcholine receptor made up of in foetal skeletal muscle?

Alpha 1
Gamma
Beta 1
Alpha 1
Delta

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What’s the difference in function between nicotinic acetylcholine receptors in adult and foetal skeletal muscle

Adult- channel is open longer and brings in different molecules

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What is the nicotinic acetylcholine receptor made up of in the CNS?

Alpha 2-4 and beta 2-4

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Give symptoms of myasthesia gravis

muscle weakness
drooping eyelids
Fatigue
difficulty swallowing or talking
exertion is hard

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What causes myasthesia gravis?

Muscle nicotinic acetylcholine receptors become degraded

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What subunit does myasthesia gravis target?

The alpha 1 subunit

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How much of the proteome is made up of G protein coupled receptors?

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Roughly what proportion of all pharmaceutical drugs target GPCRs?

30%

What subunits make up a GPCR?

Alpha, beta gamma (and GDP?)

What happens when the agonist binds to the GPCR?

There is a change in the affinity of the alpha subunit, so it binds to GTP which activates it

What happens when the alpha subunit is activated in GPCRs?

It dissociates from the beta gamma and interacts with other proteins

How many transmembrane domains do GPCRs have?

What does the alpha s do from GPCRs?

Stimulates

What does the alpha I do from GPCRs?

Inhibits adenyl cyclase

What does the alpha q do from GPCRs?

Interacts with the PLC beta

What does the alpha 12/13 interact with from GPCRs?

RhoGEF

What does adenylate cyclase do with alpha I?

Takes ATP-> activated pKA (v.basic)

What does phosphodiesterase break down?

cAMP

What does Gq/11 do?

Increased phospholipase C activity

What does PIP2 stand for?

Phosphatidylinositol

What does IP3 stand for?

Inositol triphosphate

What does DAG stand for?

Diacylglycerol

What is tyrosine receptor kinase involved in?

Insulin Epidermal growth factor (EGF) Platelet derived growth factor (PDGF)

What is JAK/STAT involved in?

Growth hormone | Interferon

What is serine threonine receptor kinase involved in?

TGF beta

What are nuclear receptors involved in?

Glucocorticoid | Thyroid hormone

What are enzyme-linked receptors involved in the regulation of?

``` Cell growth Division Differentiation Survival Migration ```

What is inappropriate enzyme linked receptor activity associated with?

Disease including cancer

What does activation of enzyme-linked receptors lead to?

Actuation of receptor kinases | Activation of multiple signalling pathways

What does dimerisation of tyrosine kinase linked receptors do?

Brings together two receptor molecules allowing autophosphorylation of specific tyrosine residues

Can all tyrosine residues be phosphorylated?

What does phosphorylation of tyrosine residues form?

Docking domains

What do the proteins that bind to the docking domain of tyrosine kinase linked receptors recognise?

A specific AA sequence that includes a phosphorylated tyrosine residue

What is a motif in tyrosine kinase linked receptors?

Specific AAs including a phosphorylated tyrosine residue

What happens when grb-2 binds to the tyrosine through its SH2 domains?

Undergoes a conformational change which allows it to bind to another protein called GEF through the SH3 domain

How is RAS GTP made from GEF?

RAS binds to GEF | GDP swapped for GTP

What is ras?

Membrane associated protein that is bound to GDP

What does PI3-kinase phosphorylate?

PIP2 to PIP3

What does the insulin receptor consist of?

2 alpha chains | 2 beta chains

What are the subunits joined by in insulin receptors?

Disulfide bridges

What happens to the insulin receptors when the insulin isn’t bound?

It doesnt allow the phosphorylation of receptors

What happens in the insulin receptor when insulin is bound

There is a conformational change to the receptor which allows autophosphorylation to take place

How does the insulin receptor substrate bind in the insulin receptor?

SH2 domain

What do insulin receptors lead to in the liver and muscles?

Glycogen synthesis or protein synthesis

What can insulin receptors lead to?

Stimulation of glucose transporters which increase glucose uptake

What other proteins can insulin substrates recruit

Ras and phospholipase c

How are phosphatase activated?

As a result of the receptor activation

What do kinases add?

Phosphates

What do phosphatase remove?

Phosphates

What facilitates the inactivation of the molecules?

PTEN

What enzyme is ras acted on by to speed up the inactivation?

GTPase activating protein (GAP) binds to the activated Ras and stimulates the GTPases which leads to the dissociation of GTP

What can mutations in key regulatory mechanisms lead to?

Increase in receptor expression Loss of phosphatase activity Loss of GTPase activity Loss of phosphatase activity

What is jak-STAT signalling pathway activated by?

Growth hormone

Give the JAK-STAT signalling pathway

Jaks cross-phosphorylate each other on tyrosine Activated jaks phosphorylate receptors on tyrosine STATs dock on phosphotyrosines and jaks phosphorylate them STATs dissociate from receptors and dimerise via SH2 domain Travels to the nucleus where it will stimulate and regulate the gene regulatory protiens

What does the serine-threonine kinase require the presence of?

Two different types of receptor

What is the serine-threonine kinase domain?

Type 2 receptor, by binding of TGF beta undergoes a conformational change

What are intracellular receptors activated by?

Molecules that readily pass across the cell membrane and are largely insoluble in aqueous environments

Give some intracellular receptor activators

Thyroid and steroid hormones and glucocorticoids

What are the intracellular receptor activators delivered bound to?

Globulin including vit D

In steroid receptors what does the binding of cortisol to a glucocorticoid receptor lead to?

Dissociation of the heat shock protein and the glucocorticoid receptor bound to the cortisol

What does the glucocorticoid receptor- cortisol complex do in the nucleus?

Binds with the glucocorticoid response element which leads to an increase in gene transcription

How do thyroid hormone receptors work?

T3 delivered to the cell bound to a binding globulin. Then it diffuses across the plasma membrane into the nucleus where it binds to the thyroid hormone receptor