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G protein-coupled receptors has __ transmembrane domains
7
Different physiological responses carried out by GPCR
Vision, Taste, sense of smell, reproduction, parasympathetic & sympathetic nervous system, etc
How many subunits is a GP composed of
3
What is the names of the GP subunits
Alpha, Beta, Gamma
What is the function of GTPase
hydrolyzes GTP to GDP and make alpha subunit dissociate from AC
Which subunit of G protein contains GTPase
Alpha
What is the function of Adenylyl cyclase(AC)
Convert ATP to cAMP
What is the function of cAMP
activates protein kinase A (PKA)
which type of G protein is coupled with opioid receptors?
Gi (inhibits pain signaling)
How is Gi protein activated?
ligand binds, GTP binds to GTP/GDP binding site on alpha subunit, alphai-GTP dissociate from Beta-Gamma and bind to AC to inhibit activity.
What affects do Gi proteins have on intracellular cAMP levels?
Reduced levels
Adenylyl cyclase has ___ transmembrane domains
12
How many molecules of cAMP bind to PKA regulatory subunits?
4, 2 in each
what is the function of kinase
add phosphate group to target protein which may activate or inhibit target activity
What are 3 substrates of PKA
Lipase, glycogen synthase, phosphorylase kinase
Does a phosphodiesterase inhibitor increase or decrease intracellular levels of cAMP?
Increase
What is the function of a phosphodiesterase
converts cAMP to AMP
What 3 things does PKC require for activation?
Ca+2, DAG, Phosphatidylserine (PS)
T/F: G-protein mediated activation can only be carried out by the alpha subunit.
False, Beta gamma subunit activates K+ channel
What are the different types of kinases and what G protein uses them
PKG for Gt, PKA for Gs, PKC for Gi
What are some different second messengers and where are they used
cGMP for Gt, cAMP for Gs, IP3 and DAG for Gi
Name the similarities between cholera toxin (cholera) and pertussin toxin (whooping cough)
Causes ADP-ribosylation, high cAMP levels
What Gprotein does cholera attack
Gs alpha subunit
What Gprotein does pertussis attack
Gi alpha subunit
What does cholera impair
GTPase activity
What does pertussis impair
GTP/GDP exchange
What does impairment of the GTPase activity cause
alpha S- GTP is permanently bound to AC and production of cAMP is consistent causing efflx of Cl and other electrolytes
What does impairment of the GTP/GDP exchange cause
Gi protein is bound with GDP and can NOT bind to AC which leads to high cAMP levels which will lead to interference of recruitment for immune responses
What are the mechanisms of homologous desensitization
Receptor gets activated, phosphorylation of receptor, arresting binds to phosphorylated receptor, loss of G protein or swallowing of receptor
T/F Desensitized nACh receptors have reduced affinity
False
What receptors have lower affinity after rapid desensitization
Beta-adrenergic receptors
What receptors have increased affinity after rapid desensitization
nACh receptors
Examples of kinase-linked receptors
Epidermal growth factor, insulin, atrial Natriuretic peptides, Erythropoietin
Primary function of Kinase-linked receptors
regulation of growth of cells/tissues
Key structural features of kinase-linked receptors
Single transmembrane domain, kinase domain cytoplasmic tail, cysteine domain or immunoglobulin domain in extracellular space
What makes Kinase-linked receptor signaling unique
autophosphorylation, ligand binding, receptor dimerization, recruitment of adaptor proteins
What adaptor proteins mediate kinase-linked receptor signaling
Grb2, SOS, Shc, Ras
what do adaptor proteins for kinase-linked receptor signaling have in common
SH2 Domain
Grb2 definition
Growth factor-receptor-binding protein 2
SOS definition
Son of Sevenless
Shc definition
SRC homology 2 domain containing transform protein
Ras definition
Small GTPase
Lists two major functions of insulin receptor
Stimulates uptake of glucose into cells, gene expression, and mitogenic signaling
Function of Epo receptor
stimulate RBC maturation
What is unique about Epo signaling pathway
Exists as a dimer that has autophosphorylation occur at the Jak2 protein
function of Natriuretic peptide
Vasodilation and salt/water excretion for decreased blood pressure and volume
What is unique about the natriuretic peptide receptor
Cytoplasmic tail contains guanylyl cyclase that converts GTP to cGMP
What does guanylyl cyclase do
converts GTP to cGMP
What is the role of nuclear receptors in the body
suppress inflammation and immune responses, electrolyte balance, thyroid function, Vitamin D, reproduction, metabolism, insulin sensitivity
List homodimer nuclear receptors
cortisol, aldosterone, estrogen, progesterone, testosterone
List heterodimer nuclear receptors
Thyroid, retinoic acid, vitamin D3, PPAR(alpha), PPAR(gamma)
what is the name of the DNA binding domain of nuclear receptors
Zinc fingers
What is the function of the amino acids in Box 1 of zinc fingers
Specificity (glucocorticoid vs estrogen)
What is the function of the amino acids in Box 2 and 3 of zinc fingers
Dimerization of 2 receptors
what does activating PPAR receptors cause
Adipocyte differentiation, increased insulin sensitivity, increased lipid metabolism
PPAR alpha agonist include
clofibrate, gemfibrozil, fenofibrate
PPAR gamma agonist include
rosiglitazone, pioglitazone
what nuclear receptor is responsible for lipid metabolism
PPAR alpha
what nuclear receptor is responsible for insulin sensitivity
PPAR gamma
what nuclear receptor is responsible for Calcium absorption
Vitamin D3
what nuclear receptor is responsible for electrolyte balance
aldosterone
what nuclear receptor is responsible for immune response
Cortisol
how many transmembrane domains in kinase-linked receptors
1