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.

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
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.

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
3
Q

What uses second messengers?

A

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

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
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.

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
5
Q

What is phosphorylation

A

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

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
6
Q

What rapidly removes protein phosphates from proteins

A

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

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
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.

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
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.

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
9
Q

What activates G protein

A

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

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
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

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
11
Q

Signal transduction usually contains…

A
  • multi-step pathways that provide opportunities for co-ordination and regulation of the cellular response
How well did you know this?
1
Not at all
2
3
4
5
Perfectly
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

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
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)
How well did you know this?
1
Not at all
2
3
4
5
Perfectly
14
Q

What does G protein stand for?

A

Guanine nucleotide binding protein

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
15
Q

Structure of G-protein

A

Heterotrimerie - 3 different subunits

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
16
Q

Which subunit is most important for signal transduction

A
  • alpha subunit
How well did you know this?
1
Not at all
2
3
4
5
Perfectly
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
How well did you know this?
1
Not at all
2
3
4
5
Perfectly
18
Q

Different types of _____ ______ produce different ________

A

Different types of alpha subunits produce different signalling

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
19
Q

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

A
20
Q

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

A
21
Q

Glucagon receptor signal transduction

A
22
Q

GLP-1 receptor signal transduction

A
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
Q

What is exendin-4 (exenatiide) used for?

A

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
Q

Why can’t we used GLP-1 itself? Instead of exenatide

A
  • 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
Q

Signal transduction for RTKs - diagram of structure

A
28
Q

How do receptor tyrosine-kinases (RTK) start signal transduction?

A
  • using phosphorylation of so-called adaptor proteins to start signal transduction
29
Q

Difference between signal transduction starting for RTKs and GPCR

A
  • RTKs major way is phosphorylation where as for GPCR’s they use second messenger then phosphorylation
30
Q

Process of signal transduction for RTKS

A
  • agonist Lingnan binds
  • receptor changes conformation and becomes activated
  • receptors autophosphosphorylation occurs
  • adaptor protein is phosphorylated
  • thus causing events
31
Q

For RTKs what is the part of the signal transduction pathway that communicates with other proteins in the cell?

A

Adaptor proteins

32
Q

There are different types of ______ _____, which have different effects

A
  • adaptor proteins
33
Q

Why can tkr self phosphorylate

A

Receptor has a kinase within its self

34
Q

RTK example - insulin receptor signal transduction - muscle and adipose

A
  • 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
Q

Insulin receptor transduction in liver cells

A
  • 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
Q

Signal transduction - Ligand-gated ion channels - process

A
  • 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
Q

Signal transduction Responses are controlled by…

A

…where receptors are expressed e.g liver vs muscle

38
Q

Different cells have different _______ of receptors and _____ molecules, allying cells to ____ and _____ differently to different ______

A

Different cells have different collections of receptors and relay molecules, allowing cells to detect and respond differently to different ligands

39
Q

Can the same ligand/receipt or pairing have different effects in different cells ?

A

Yes

40
Q

why can the same ligand/receptor pairing have different effects in different cells?

A

Because they use different combinations of relay molecules for signal transduction

41
Q

What can further help the call co-ordinate signals from incoming ligands?

A

Pathway branching and “cross-talk”

42
Q

Digaram the illustrates how cells can produce different responses (4 diff cell types) - YAPP

A
  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
  2. 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
  3. Second receptor activates its own chain of events leading to a unique response
43
Q

What is a receptor

A

A cellular protein (or assembly of proteins) that control chemical signalling between and within cells

44
Q

What is a ligand

A

The general term given to a chemical substance that specifically binds to a receptor

45
Q

What is an agonist

A

A chemical substance (ligand) that binds to a receptors and activates it

46
Q

Antagonist

A

A chemical substance (ligand) that binds to a receptor and prevents activation by an agonist