Hormone Receptors and Intracellular Signaling

Question 1

Four categories of receptors?

Answer 1

1. ) Ligand-gated ion channels
2. ) G-protein-coupled receptors
3. ) Catalytic receptors
4. ) Nuclear receptors

Question 2

What are ligand-gated ion channels?

Answer 2

Hybrid receptors with an ion channel

Question 3

What are G-protein-coupled receptors?

Answer 3

Protein receptors that work through G-heterotrimeric complexes to activate/inactivate intracellular effects

Question 4

What are catalytic receptors?

Answer 4

Protein receptors that are either enzymes or part of an enzyme complex

Question 5

What are nuclear receptors?

Answer 5

Protein receptors that are located either in the cytoplasm or in the nucleus and alter gene expression

Question 6

How do ligand-gated ion channel receptors work?

Answer 6

A neurotransmitter binds to the extracellular portion of the receptor allowing it to open and allow ions in

Question 7

What two things can G-proteins be?

Answer 7

Either inhibitory or stimulatory

Question 8

Which subunits are stimulatory and inhibitory respectively?

Answer 8

Stimulatory: alpha-s
Inhibitory: alpha-i

Question 9

How do G-protein receptors work?

Answer 9

1. ) inside the cell there is an alpha-beta-gamma complex
2. ) Ligand binds to the receptor
3. ) Alpha unit breaks off to activate adenylyl cyclase
4. ) AC converts ATP to cAMP
5. ) cAMP activates PKA
6. ) PKA phosphorylates proteins either inhibiting or stimulating them

Question 10

What occurs when a G-protein coupled to alpha-t is activated?

Answer 10

The enzyme phosphodiesterases (PDE) is activated which then turns cGMP to GMP (closure of cGMP-dependent channels)

Question 11

How does the cholera toxin work?

Answer 11

Enters intestinal epithelium and binds with the G-alpha-s subunit and inhibits the GTPase so that G-alpha-s stays active increasing Cl- conductance and fluid movement into intestines

Question 12

What is an example of catalytic receptors?

Answer 12

Receptor Tyrosine Kinases (RTKs)

Question 13

How do RTKs work?

Answer 13

When a ligand binds to the extracellular domain RTK dimerizes and autophosphorylates itself allowing it to phosphorylate other proteins inside the cell

Question 14

How does the JAK-STAT pathway work?

Answer 14

1. ) JAK is on the intracellular RTK
2. ) Ligand binds
3. ) JAK phosphorylates STAT (transcription factor)
4. ) Phosphorylated STAT protein dimerizes
5. ) STAT dimer enters the nucleus and binds DNA response elements stimulating gene expression

Question 15

Three pathways which the plasma membrane receptors can send signals to the cytoplasm to initiate immediate effects and to the nucleus to initiate long-term effects?

Answer 15

1. ) cAMP dependent pathway
2. ) Ras-MAPK dependent pathway
3. ) JAK-STAT pathway

Question 16

All GPCR have what steps in common?

Answer 16

Up to PKA activation; afterwards it may get more specific

Question 17

What amino acid residues does PKA phosphorylate?

Answer 17

Serine

Threonine

Question 18

What two ways can a GPCR activation be terminated?

Answer 18

1. ) Phosphodiesterases in the cell degrade cAMP

2. ) Serine/threonine-specific protein phosphatases can dephosphorylate enzymes and proteins

Question 19

What does PKA cause in osteoblasts?

Answer 19

Release of IL-6 and RANK-L which then stimulates pre-osteoclasts to become mature osteoclasts

Question 20

How do inhibitory GPCR work?

Answer 20

The alpha-i inhibits AC from forming cAMP

Question 21

What catecholamine receptors are stimulatory?

Answer 21

Beta-1
Beta-2
Dopamine-1

Question 22

What catecholamine receptors are inhibitory?

Answer 22

Alpha-2

Dopamine-2

Question 23

What does the GPCR Gq act on?

Answer 23

Stimulates phospholipase C (PLC)

Question 24

What are the steps in Gq activation?

Answer 24

1. ) Gq bound
2. ) Alpha subunit activates PLC
3. ) PLC cleaves PIP2 into IP3 and DAG
4. 1) IP3 opens Ca2+ channels intracellularly
5. 2) DAG activates PKC
6. ) PKC can phosphorylate stuff

Question 25

Tyrosine kinase receptor Ras-MAPK pathway:

Answer 25

1. ) Ligand binds tyrosine kinase
2. ) RTK autophosphorylates
3. ) SH2 domain of the GRB2 binds to the RTK
4. ) GRB2 bind recruits SOS
5. ) SOS activates RAS by switching GDP for GTP bound to RAS
6. ) Active GTP-RAS recruits/activates Raf-1
7. ) Raf-1 phosphorylates and activates MEK
8. ) MEK phosphorylates and activates MAPK
9. ) MAPK phosphorylates many proteins
10. ) MAPK translocates to the nucleus to phosphorylate transcription factors

Question 26

What type of disease is Noonan Syndrome?

Answer 26

RASopathy (a disruption in RAS-MAPK pathway)

Question 27

What specifically causes Noonan Syndrome?

Answer 27

Mutation in SOS1

Question 28

Noonan syndrome symptoms:

Answer 28

Webbed neck

Double structural curve (scoliosis) with rib deformity

Question 29

What is the insulin RTK receptor (IGF-1) composed of?

Answer 29

An alpha chain extracellularly and a beta chain intracellularly

Question 30

What do the alpha and beta chains of the IGF-1 contain respectively?

Answer 30

Alpha: cysteine-rich domain for binding insulin
Beta: Tyrosine kinase activity

Question 31

What does growth hormone bind to?

Answer 31

JAK-STAT growth hormone receptor

Question 32

What hormone is the main contributor to growth short and long term?

Answer 32

Short term: GH (Growth hormone)

Long term: IGF-1 (insulin growth factor 1)

Question 33

What is Laron’s syndrome?

Answer 33

An autosomal recessive disorder characterized by an insensitivity to growth hormone (mutant growth hormone receptor)

Question 34

How do glucocorticoid hormones act on the DNA?

Answer 34

1. ) Enters the cytosol
2. ) Binds to cytoplasmic receptor (cytoplasmic receptor is held by a chaperone)
3. ) Cytoplasmic receptor/glucocorticoid complex released by the chaperone
4. ) Free complex translocates to the nucleus and dimerizes
5. ) Dimer binds to the GRE and stimulates transcription (glucocorticoid responsive element)

Question 35

How do thyroid hormones act on the DNA?

Answer 35

1. ) Hormone is either transported or just diffuses across the cell membrane
2. ) Binds to thyroid hormone receptor in the nucleus
3. ) Bound thyroid receptor forms a heterodimer with retinoid x receptor
4. ) Complex binds to HRE (Hormone Response Element)