Tyrosine Kinase receptors, ion channels, and intracellular receptors

Question 1

What do the extracelllar and intracellular domains contain in the kinase linked receptors?

Answer 1

extracellular domain = recognition site for homrones, cytokines and growth factors

intracellular domain = contains kinase catalytic domain

Question 2

Describe the processs of kinase linked receptors

Answer 2

1. growth factor/hormone bind to receptors linked to tyrosine kinase
2. signal transduction involves ligand induced dimerization of the receptors followed by autophosphorylation of the tyrosine residues
3. the phospho tyrosine resides act as acceptors for specific domains (SH2) of intracellular proteins involved in the regulation of cell function

Question 3

What is the role of adapter proteins in tyrosine kinase linked sygnaling?

Answer 3

adapter proteins link signalling molecules together - they are like voltage adapters when traveling abroad - they don’t actually play a role in signalling, they just link.

Question 4

What are the roles of scaffolds in signal transmission?

Answer 4

scaffold proteins ensure that signaling molecules are in the right location - they act to speed up signalling

Question 5

What kind of protein is Ras?

Answer 5

Ras is a G protein - known as a small GTPase - monomeric protein

Question 6

mutations in Ras are involved with what disease?

Answer 6

many cancers

Question 7

what enzyme activates Ras?

Answer 7

SOS

Question 8

What does Ras activate?

Answer 8

it activates MEK which further activates ERK - which is semi-responsible for gene transcription

Question 9

What commonly dimerizes with the EGF (estrogen growth factor) receptor?

Answer 9

HER2- which is why HER2 is associated with breast cancer

Question 10

By what mechanism can we inhibit tyrosine kinase receptors?

Answer 10

1) we can block dimerization disallowing the signal
2) we can inhibit the kinase activity - disallowing the signal
3) or drugs can work further downstream in the signal (i.e. MEK or Erk)

Question 11

what is the most common enzyme linked receptor?

Answer 11

tyrosine kinase linked receptors

Question 12

what receptor is similar in structure to tyrosine kinase receptors, but is linked to guanylate cyclase?

Answer 12

Atrial Natruretic Peptide

Question 13

give an example of an ion-channel linked receptor

Answer 13

nicotinic acetylcholine receptor (nAChR)

or

GABA(A) receptor

Question 15

describe the differences between the four types of ion channels

Answer 15

1. voltage gated - triggered by change in voltage
2. ligand gated - extracellular ligand gated
3. ligand gated - intracellular ligand induced
4. stress activated - physically pushed open?

Question 16

What are the three major types of ligand gated ion channels?

Answer 16

1. P2X- ATP receptor
2. Nicotine receptor-like family - positive/negative ion channels
3. glutamate receptor like fmaily - AMPA receptor, NMDA

Question 17

Describe the mechanism of nAChR receptor

Answer 17

• ACh binds nACh receptor on the a subunit
• Channel opens and allows influx of Na+/ K+ ions into channel across membrane
• nAChR gates for positive ions
• Eventual response - muscle contraction

•

Question 18

what does an agonist vs. antagonist do to a channel?

Answer 18

agonist: facilitates opening

antagonist = prevents opening

Question 19

Give an example of a

positive ion receptor channel

and a

negative ion receptor channel

Answer 19

positive ion receptor channel = nAChR

negative ion receptor channel = GABA(A) receptor

Question 20

What type of channel is the GABA (A) receptor? - where is it found? what does it bind?

Answer 20

• Cl- ion channel receptor
• Cl- flux following activation by GABA binding
• Found mainly in CNS
• Binds multiple ligands

–GABA

–Benzodiazepines

–Ethanol

–Barbiturates

Question 21

Describe the effect of alocohol on your GABA receptors

Answer 21

GABA + Ethanol - increases the amount of chlorine allowed through the channel - this leads to a shut down of the ‘stupidity’ center of your brain

• in an alcoholic, the brain notices that there is much more chloride coming into the brain and limits number of GABA receptors over time building up a tolerance to the ethanol effects. If you are to ‘cut cold turkey’ your brain may not recieve the chloride it requires - this is potentially very dangerous

Question 22

Describe the effect of Benzodiazepine on GABA receptors

Answer 22

Benzodiazepines bind to an allosteric site of GABA (a) receptors and facilitate the binding of GABA -

Question 23

What is Tubocurarine used for? What receptor does it act on?

Answer 23

tubocurarine acts on the nAChR - and causes paralysis and stops breathing - use when someone is on the respirator to prevent them from breathing while the respirator is on

Question 24

Describe the mechanism of action of the glucocorticoid receptor

Answer 24

• heat shock protein [hsp90] bound to receptor in absense of hormone - prevents folding into actibe conformation of the receptor
• binding of a hormone causes dissociatoin of the hsp 90 - permits conversion to active conformation
• activated receptor can now initiate transcription of the target gene
  *

Question 25

what are heat shock proteins ? What do they do?

Answer 25

heat shock proteins are chaperones - they prevent denaturing of proteins and are involved in the facilitating of folding

Question 26

What does SERM stand for?

Answer 26

selective estrogen receptor modifier

Question 27

What do we use SERMs for? Give an example of a SERM

Answer 27

Selective estrogen receptor modifiers (SERM) - are used in certain types of breast cancers that are driven by estrogen - estrogen is a growth factor so we block the estrogen receptors and prevent growth.

ex) tamoxifen - binds to the estrogen receptors in breast AND uterine tissue (but in uterus it stimulates instead of inhibiting)