Term
The three largest classes of cell surface receptors |
|
Definition
1.Ion-channel linked receptors
-rapid synaptic signaling between electrically excitable cells
-mediated by neurotransmitters
2. G-protein-coupled receptors
-indirectly regulate the activity of membrane-bound target proteins
-mediated by a trimeric GTP-binding protein (trimeric G-protein)
3. Enzyme-coupled receptors
-either function as enzymes or are linked with enzymes
-heterogeneous class
-most are protein kinases (or associated with protein kinases)
|
|
|
Term
|
Definition
-seven short hydrophobic stretches form transmembrane alpha helices
-connected by alternating extracellular and intracellular loops
-Called “7-pass” transmembrane receptors
|
|
|
Term
Trimeric G proteins relay the signals from GPCRs to other intracellular signaling proteins |
|
Definition
•Trimeric G proteins
-3 subunits; alpha, beta and gamma
-Attached to the plasma membrane
-The G alpha binds a guanyl nucleotide
-Various types, each specific for a set of GPCRs and for a particular downstream target, but they all operate the same way
|
|
|
Term
The trimeric G- proteins act as molecular switches |
|
Definition
GTPases two states
-Inactive; Ga bound to GDP. trimer of a, b, and g.
-Active; Ga bound to GTP.
-Trimer may dissociate to yield Ga-GTP and
G-bg or confirmation change, but subunits stay together
-
-Several flavors of trimeric G-proteins
Gs: A G-protein which acts to stimulate a target enzyme (G stimulatory )
Gi: acts to inhibit a target enzyme (G inhibitory)
-
|
|
|
Term
Ligand binding to GCPR and cAMP regulation |
|
Definition
-ligand binding to a GPCR can lead to a rise in intracellular cAMP via regulation of adenylyl cyclase
-•Binding site for adenylyl cyclase is
Unmasked
•Gsa binds to adenylyl cyclase
•cAMP is synthesized
then
•Gsa hydrolyzes GTP to GDP
• This causes Gsa to dissociate from
adenylyl cyclase
•Trimeric G-protein goes back to
“off”
•Adenylyl cyclase goes back to “off”
|
|
|
Term
|
Definition
-The hormone/receptor complex must be deactivated to return to the unstimulated state.
-carboxy terminal tail of the receptor becomes phosphorylated
-phosphorylated tail is bound by proteins (arrestins) which
sterically block receptor/G-protein interaction.
-Hydrolysis of GTP leads to inactivation of the trimeric G-protein
-enhanced by target enzyme
-enhanced by RGS proteins
(regulator of G-protein signaling)
|
|
|
Term
cAMP exerts its effects mainly by....... |
|
Definition
-cAMP exerts its effects mainly by activating cyclic-AMP-dependent protein kinase (PKA)
-Accounts for most effects of cAMP in most cell types
- Serine/threonine kinase
Two types; cytosol or anchored to membranes
|
|
|
Term
PKA targets can be cytoplasmic or nuclear
|
|
Definition
1.Cytoplasm
-PKA targets are often enzymes involved
in metabolic pathways
2.Nucleus
-PKA can modify gene regulatory proteins to
alter gene expression
Example; phosphorylation of CREB
(cAMP response element binding protein)
- PKA catalytic subunits move into
the nucleus
-PKA phosphorylates CREB
-Phosphorylated CREB recruits histone acetyl
transferases (HAT)
- transcription is initiated
|
|
|
Term
The life and death of cAMP; terminating the signal |
|
Definition
- cAMP phosphodiesterases (PDEs)
-The only means of degrading cAMP
-Inhibitors of PDEs
Non-selective inhibitors: Xanthines
caffeine and theophylline
|
|
|
Term
b-blockers: b1 antagonists
|
|
Definition
b1 receptors found in cardiac muscle, promote increased heart rate
- b1 antagonists slow heart rate and are b1 selective
-treat ailments associated with stress; high blood pressure, angina, irregular heart rhythms, migraines
-prevention of second heart attacks
-acebutolol, atenolol, metoprolol (lopressor)
|
|
|
Term
Chronic PTH vs Intermittent PTH |
|
Definition
Chronic leads to bone resorption
Intermittent leads to bone formation |
|
|
Term
Alterations to the parathyroid hormone receptor in human disease |
|
Definition
Jansen’s metaphyseal chondrodysplasia
-rare
-short-limbed dwarfism
-severe growth plate abnormalities, increased bone
resorption with normal/low levels of PTH
-two point mutations identified
-constitutive activity of the PTHR (agonist-independent)
-mutations alter receptor conformation to “on”
|
|
|