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14 Flashcards

1
Q

Active receptor starts a chain of
events where messages are passed
on through the cell via a process
called

A

signal transduction.

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2
Q

How can a message be passed on? In signal transduction

A

The message can be passed on
using proteins, chemical signals
called second messengers , or
through sequential phosphorylation.

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3
Q

What uses second messengers?

A

Many different receptors, especially G protein-coupled
receptors use second messengers.

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4
Q

How do second messengers work?

A

Second messengers can transmit signals from a receptor
to other relay molecules because they are not attached to
the membrane and are free to move in the cell.

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5
Q

What is phosphorylation

A

Widespread mechanism for regulating protein activity where
protein kinases transfer phosphates from ATP to protein
(phosphorylation).

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6
Q

What rapidly removes protein phosphates from proteins

A

Protein phosphatases rapidly remove the phosphates from
proteins (dephosphorylation) to carefully control signal transduction.

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7
Q

What does signal transduction pathways use to relate a phosphorylation cascade

A

Signal transduction pathways often use many different
protein kinases, creating a phosphorylation cascade.

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8
Q

What are GPCRS? What do they use to start signal transduction?

A

G protein-coupled receptors (GPCRs) use G proteins to
start signal transduction, hence their name.

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9
Q

What activates G protein

A

The GPCR activates the G protein, which communicates
with other proteins in the cell.

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10
Q

The different types of G proteins and the different effects

A

Gα s = stimulatory G protein, which activates an enzyme called adenylate cyclase Gαi = inhibitory G protein, decreases the activity of adenylate cyclase

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11
Q

Signal transduction usually contains…

A
  • multi-step pathways that provide opportunities for co-ordination and regulation of the cellular response
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12
Q

What does phosphorylation and dephospylation do?

A

Phosphorylation and dephosphorylation events turn protein activity on and off or up to down as required

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13
Q

How is signal transduction tightly regulated to control cellular activity?

A
  1. Ligand dissociation (makes receptor inactive)
  2. Internalisation - receptor is removed from the cell surface through endocytosis so it can no longer respond to ligand
  3. Phosphatases - (removal of group to turn off activity of a kinase)
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14
Q

What does G protein stand for?

A

Guanine nucleotide binding protein

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15
Q

Structure of G-protein

A

Heterotrimerie - 3 different subunits

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16
Q

Which subunit is most important for signal transduction

A
  • alpha subunit
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17
Q

What is the G-protien cycle?

A
  • the way the G protein is activated and inactivated
  • exchange of GTP and GDP on guanine nucleotides
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18
Q

Different types of _____ ______ produce different ________

A

Different types of alpha subunits produce different signalling

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19
Q

Diagram of singnal transduction for a ‘Gs-coupled’ GPCR - hand drawn

20
Q

Diagram of singnal transduction for a ‘Gs-coupled’ GPCR

21
Q

Glucagon receptor signal transduction

22
Q

GLP-1 receptor signal transduction

23
Q

How did we discover drugs that targeted the GLP-1 receptor?

A

Discovered form natural research into the biological effects of venoms

24
Q

What was the chemical in venom extracted?

A

Extendin-4 (exenatide)

25
What is exendin-4 (exenatiide) used for?
The exendin-4 (exenatide) peptide had similar amino acid sequence to GLP-1 and acted as a GLP-1 receptor agonist so synthetic exendin-4 is used as a diabeties drug, called byetta
26
Why can’t we used GLP-1 itself? Instead of exenatide
- rapidly broken down in the blood stream (It is produced, stays around long enough to have its effect and is then broken down and removed) - extendin-4 peptide isn’t broken down as fast
27
Signal transduction for RTKs - diagram of structure
28
How do receptor tyrosine-kinases (RTK) start signal transduction?
- using phosphorylation of so-called adaptor proteins to start signal transduction
29
Difference between signal transduction starting for RTKs and GPCR
- RTKs major way is phosphorylation where as for GPCR’s they use second messenger then phosphorylation
30
Process of signal transduction for RTKS
- agonist Lingnan binds - receptor changes conformation and becomes activated - receptors autophosphosphorylation occurs - adaptor protein is phosphorylated - thus causing events
31
For RTKs what is the part of the signal transduction pathway that communicates with other proteins in the cell?
Adaptor proteins
32
There are different types of ______ _____, which have different effects
- adaptor proteins
33
Why can tkr self phosphorylate
Receptor has a kinase within its self
34
RTK example - insulin receptor signal transduction - muscle and adipose
- glut 4 (glucose transporter) gets translocated to cell surface - receptor activation causes phosphorylation of an “adaptor” protein, and further signal transduction events, leading to GLUT-4 transocation - muscle and adipose cells - insulin is an example of a peptide ligand
35
Insulin receptor transduction in liver cells
- in liver cells, receptor activation causes phosphorylation of an “adaptor” protein, and further signal transduction events, this time leading to glycogen synthesis - different things can happen in different cell types
36
Signal transduction - Ligand-gated ion channels - process
- ligand-gated ion channels are slightly different to other receptors - an agonist ligand that binds causes a conformational change to activate the receptor - instead of ‘relay’ proteins like G proteins or adaptors being used, ions directly flow through the channel to produce effects - these receptors produce fast signalling, compared to the slower signalling of CPCRs and RTKs (- ionaptropic means fast singalong of ion channels - meta-tropic means slow via gprotein )
37
Signal transduction Responses are controlled by…
…where receptors are expressed e.g liver vs muscle
38
Different cells have different _______ of receptors and _____ molecules, allying cells to ____ and _____ differently to different ______
Different cells have different collections of receptors and relay molecules, allowing cells to detect and respond differently to different ligands
39
Can the same ligand/receipt or pairing have different effects in different cells ?
Yes
40
why can the same ligand/receptor pairing have different effects in different cells?
Because they use different combinations of relay molecules for signal transduction
41
What can further help the call co-ordinate signals from incoming ligands?
Pathway branching and “cross-talk”
42
Digaram the illustrates how cells can produce different responses (4 diff cell types) - YAPP
1. Receptor is activated by ligand producing a particular chain of events leading to a cellular response 2+3. Same receptor is expressed and responding to same ligand but get a different response due to pathway branching where receptor activates first same pathway protein but then goes on to two different down stream proteins in this particular cell type resulting in a unique response 4. Two different receptors coming into play which co-ordinate each others activities - second receptor activates its own unique signal transduction pathway which has cross talk with signal transduction pathway of the other receptor leading to a unique response 5. Second receptor activates its own chain of events leading to a unique response
43
What is a receptor
A cellular protein (or assembly of proteins) that control chemical signalling between and within cells
44
What is a ligand
The general term given to a chemical substance that specifically binds to a receptor
45
What is an agonist
A chemical substance (ligand) that binds to a receptors and activates it
46
Antagonist
A chemical substance (ligand) that binds to a receptor and prevents activation by an agonist

BIOC192 (38 decks)

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