Hormone Receptors and Intracellular Signaling Flashcards
Four categories of receptors?
- ) Ligand-gated ion channels
- ) G-protein-coupled receptors
- ) Catalytic receptors
- ) Nuclear receptors
What are ligand-gated ion channels?
Hybrid receptors with an ion channel
What are G-protein-coupled receptors?
Protein receptors that work through G-heterotrimeric complexes to activate/inactivate intracellular effects
What are catalytic receptors?
Protein receptors that are either enzymes or part of an enzyme complex
What are nuclear receptors?
Protein receptors that are located either in the cytoplasm or in the nucleus and alter gene expression
How do ligand-gated ion channel receptors work?
A neurotransmitter binds to the extracellular portion of the receptor allowing it to open and allow ions in
What two things can G-proteins be?
Either inhibitory or stimulatory
Which subunits are stimulatory and inhibitory respectively?
Stimulatory: alpha-s
Inhibitory: alpha-i
How do G-protein receptors work?
- ) inside the cell there is an alpha-beta-gamma complex
- ) Ligand binds to the receptor
- ) Alpha unit breaks off to activate adenylyl cyclase
- ) AC converts ATP to cAMP
- ) cAMP activates PKA
- ) PKA phosphorylates proteins either inhibiting or stimulating them
What occurs when a G-protein coupled to alpha-t is activated?
The enzyme phosphodiesterases (PDE) is activated which then turns cGMP to GMP (closure of cGMP-dependent channels)
How does the cholera toxin work?
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
What is an example of catalytic receptors?
Receptor Tyrosine Kinases (RTKs)
How do RTKs work?
When a ligand binds to the extracellular domain RTK dimerizes and autophosphorylates itself allowing it to phosphorylate other proteins inside the cell
How does the JAK-STAT pathway work?
- ) JAK is on the intracellular RTK
- ) Ligand binds
- ) JAK phosphorylates STAT (transcription factor)
- ) Phosphorylated STAT protein dimerizes
- ) STAT dimer enters the nucleus and binds DNA response elements stimulating gene expression
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?
- ) cAMP dependent pathway
- ) Ras-MAPK dependent pathway
- ) JAK-STAT pathway
All GPCR have what steps in common?
Up to PKA activation; afterwards it may get more specific
What amino acid residues does PKA phosphorylate?
Serine
Threonine
What two ways can a GPCR activation be terminated?
- ) Phosphodiesterases in the cell degrade cAMP
2. ) Serine/threonine-specific protein phosphatases can dephosphorylate enzymes and proteins
What does PKA cause in osteoblasts?
Release of IL-6 and RANK-L which then stimulates pre-osteoclasts to become mature osteoclasts
How do inhibitory GPCR work?
The alpha-i inhibits AC from forming cAMP
What catecholamine receptors are stimulatory?
Beta-1
Beta-2
Dopamine-1
What catecholamine receptors are inhibitory?
Alpha-2
Dopamine-2
What does the GPCR Gq act on?
Stimulates phospholipase C (PLC)
What are the steps in Gq activation?
- ) Gq bound
- ) Alpha subunit activates PLC
- ) PLC cleaves PIP2 into IP3 and DAG
- 1) IP3 opens Ca2+ channels intracellularly
- 2) DAG activates PKC
- ) PKC can phosphorylate stuff
Tyrosine kinase receptor Ras-MAPK pathway:
- ) Ligand binds tyrosine kinase
- ) RTK autophosphorylates
- ) SH2 domain of the GRB2 binds to the RTK
- ) GRB2 bind recruits SOS
- ) SOS activates RAS by switching GDP for GTP bound to RAS
- ) Active GTP-RAS recruits/activates Raf-1
- ) Raf-1 phosphorylates and activates MEK
- ) MEK phosphorylates and activates MAPK
- ) MAPK phosphorylates many proteins
- ) MAPK translocates to the nucleus to phosphorylate transcription factors
What type of disease is Noonan Syndrome?
RASopathy (a disruption in RAS-MAPK pathway)
What specifically causes Noonan Syndrome?
Mutation in SOS1
Noonan syndrome symptoms:
Webbed neck
Double structural curve (scoliosis) with rib deformity
What is the insulin RTK receptor (IGF-1) composed of?
An alpha chain extracellularly and a beta chain intracellularly
What do the alpha and beta chains of the IGF-1 contain respectively?
Alpha: cysteine-rich domain for binding insulin
Beta: Tyrosine kinase activity
What does growth hormone bind to?
JAK-STAT growth hormone receptor
What hormone is the main contributor to growth short and long term?
Short term: GH (Growth hormone)
Long term: IGF-1 (insulin growth factor 1)
What is Laron’s syndrome?
An autosomal recessive disorder characterized by an insensitivity to growth hormone (mutant growth hormone receptor)
How do glucocorticoid hormones act on the DNA?
- ) Enters the cytosol
- ) Binds to cytoplasmic receptor (cytoplasmic receptor is held by a chaperone)
- ) Cytoplasmic receptor/glucocorticoid complex released by the chaperone
- ) Free complex translocates to the nucleus and dimerizes
- ) Dimer binds to the GRE and stimulates transcription (glucocorticoid responsive element)
How do thyroid hormones act on the DNA?
- ) Hormone is either transported or just diffuses across the cell membrane
- ) Binds to thyroid hormone receptor in the nucleus
- ) Bound thyroid receptor forms a heterodimer with retinoid x receptor
- ) Complex binds to HRE (Hormone Response Element)
