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54 Cards in this Set
- Front
- Back
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Which G protein subunits are anchored in the cytoplasmic leaflet? |
G-alpha and G-gamma |
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What G protein subunit interacts with the effector molecule? |
G-alpha |
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What are the components of a GPCR signaling cascade? |
1. ligand 2. GPCR 3. trimeric G-protein 4. effector (ie adenylyl cyclase) 5. second messenger (cAMP) |
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What causes the G-alpha subunit to disassociate from the effector molecule and reassociate with the G-beta and G-gamma subunits? |
Hydrolysis of the bound GTP to GDP |
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What is the most common effector enzyme and second messenger in GPCR signaling? What downstream pathway does this activate? |
Adenylyl cyclase cAMP PKA |
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What effector, downstream pathway, and function is associated with cGMP? |
Gyanylyl cyclase PKG Optical rod cells |
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What are the second messengers generated by Phospholipase C? What does each one do? |
DAG -> activates PKC IP3 -> causes release of Ca++ from ER |
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What type of receptors bind a stimulatory G-alpha protein w/ cAMP as the second messenger? |
B-Adrenergic (epinephrine R) Receptors for glucagon, serotonin, vasopressin |
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What type of receptors bind an inhibitory G-alpha protein w/ cAMP as the second messenger? |
a2-Adrenergic receptor Muscarinic ACh receptor |
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What are the subunits of PKA? What do they bind/where do they go? |
2 regulatory: bind cAMP 2 catalytic: enter nucleus and phosphorylate CREB |
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What proteins can PKA phosphorylate? |
CREB & MAPK |
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What is the signaling pathway from PKA through changes in gene expression? |
PKA -> CREB-P -> creDNA + CREB-P + CBP/p300 |
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Where is GPCR/cAMP signaling commonly used to change metabolism? What are the ligands/hormones responsible? |
Adipose, liver, skeletal muscle Glucagon & epinephrine |
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What does PKA activation do in cardiac cells? |
Increases heart rate |
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What does PKA activation do in liver and skeletal muscles? |
Mediates glycogen hydrolysis to produce glucose, and TG hydrolysis to produce FAs |
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What does cholera toxin do to GPCR signaling? What are the effects? What tissue? |
Modifies a G-alpha stimulatory subunit, which causes the subunit and adenylyl cyclase to remain active -> high cAMP -> constant PKA activity -> activation of CFTR Cl- channels -Results in Cl- anions and water to flow into intestinal lumen...diarrhea
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What does Whooping Cough bacteria (bordatella pertussis) do to GPCR signaling? What are the effects? What tissue? |
Modifies a G-alpha inhibitory subunit, which prevents GDP release -> inhibition is inhibited. Therefore high cAMP -> activated PKA -> activation of CFTR Cl- channel -> fluid loss and increased mucous secretion into lungs -Alveolar epithelial cells |
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What is the mechanism of heart failure? |
1. Elevated levels of catecholamines (epinephrine) 2. Chronic stim of B-AR/Adenylyl cyclase/PKA 3. Problems with re-sequestering Ca++ will decrease the amount that can be released -> decreases in Ca++ pools in ER will weaken subsequent contractions |
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What is the series of events in normal cardiac muscle contraction? |
Epinephrine binds B-adrenergic R -> activates GPCR -> adenylyl cyclase -> cAMP -> PKA -> phosphorylates Ryanodine receptor (in SR) and T-tubule -> Ca++ influx -> muscle contraction |
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What can be used to treat hypertension, cardiac arrhythmias, heart attacks, and heart failure? |
Propranolol ie B-blockers, which block B-AR signaling/ epinephrine signaling |
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_____ can become _____ which can be cleaved by PLC into DAG and IP3 |
PI (phosphatidylinositol) PIP2 |
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How is PKC activated? |
1. PLC causes cleavage of PIP2 into DAG and IP3 2. IP3 causes release of sequestered ER Ca++ stores 3. Ca++ helps bring PKC to the plasma membrane 4. DAG at the plasma mem activates PKC 5. PKC can now phosphorylate target proteins |
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Smooth muscle relaxation is an example of what kind of signaling? Which tissues are involved? |
Paracrine Endothelial & smooth muscle cells |
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What is the mechanism / pathway of smooth muscle relaxation in the endothelial cells? |
ACh -> GPCR -> PLC/IP3 -> Ca++ complexes with calmodulin -> activates NO synthase -> produces NO, which diffuses to smooth muscle cells |
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What is the mechanism / pathway of smooth muscle relaxation in the smooth muscle cells? |
NO -> GPCR -> Guanylyl cyclase/cGMP -> PKG -> relaxation of smooth muscle |
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What are the 3 types of single pass receptors? |
- Cytokine receptors - Receptor tyrosine kinases (RTKs) - TGFBeta receptors |
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Which type of single pass receptor has an extrinsic kinase? |
Cytokine receptor |
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What happens to single pass receptors upon ligand binding? |
DIMERIZE! |
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What is the extrinsic kinase of cytokine receptors? |
JAK |
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How is JAK activated? What domain? |
By dimerization of the cytokine receptor, which autophosphorylates on tyrosine residues on the JAK Lip domain |
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What JAK do once activated? |
Phosphorylates tyrosine residues on the intracellular domain of the receptor, which will serve as a docking site |
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Phosphotyrosine residues can serve as docking sites for which kind of domains? |
SH2, PTB Also SH3 |
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What domain allows STAT to dock with cytokine receptors? |
SH2 + phosphotyrosine (on receptor) |
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How does STAT get into nucleus? (Full pathway) |
Cytokine R -> dimerization & activation of JAK -> phosphorylation of R -> docking of STAT -> JAK phosphorylates STAT -> STAT dimerizes through SH2/phosphotyrosine domains -> dimerized STAT goes to nucleus |
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Cytokine (JAK/STAT) signaling is involved in which processes? (3) |
1. interferon signaling 2. lactation 3. hematopoietic cell differentiation |
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What signal stimulates erythropoeisis through a cytokine-JAK/STAT pathway? Where is it produced? |
Erythropoietin Kidney |
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What type of single pass receptors are associated with monomeric G proteins? |
RTKs |
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What proteins mediate the activation of G-proteins (GDP -> GTP)? |
GEF |
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What proteins mediate the inactivation of G-proteins (hydrolysis of GTP -> GDP)? |
GAP |
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What 2 proteins dock on the phosphotyrosine residues of RTKs? |
SOS and GRB2 |
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What is the pathway/mechanism of MAPK activation via RTKs? |
RTK dimerizes -> docking of SOS -> SOS binds Ras -> Ras activated (GDP->GTP) -> Ras disassociates from SOS -> Ras activates MAPK |
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What is the GEF for monomeric G protein Ras? |
SOS |
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What mutations are often associated with cancer? |
Hyperactive or constantly active Ras |
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What is the pathway of MAPK activation, starting with Ras? |
Ras -> Raf (MAPKKK) -> Mek (MAPKK) -> Erk (MAPK) all are kinases |
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What are some examples of RTK families? |
EGFR (epidermal growth factor R) VEGFR (vascular endothelial growth factor R) Insulin R |
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What is a common example of a receptor mutated in breast cancer? What type of receptor is this? What pathway does it signal through? |
HER1-4 RTK Ras-MAPK |
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What is the pathway of TGFB single pass receptor signaling? |
TGFB -> binds RIII or RII receptor (already phosphorylated) -> recruits & phosphorylates RI -> phosphorylates Smad3 -> 2 Smad3 + 1 Smad4 + importin go to nucleus |
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What protein helps Smad3 and Smad4 get to the nucleus? |
Importin |
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What are the effects of TGFB signaling? (3) |
-Secretion of extracellular matrix proteins -Secretion of proteins that inhibit serum proteases -Signals anti-growth properties |
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What is a serum protease inhibitor activated by TGFB signaling? |
PAI1 |
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What are the 2 proteins that mediate TGFB antigrowth properties? What are their specific roles? |
p15: causes cell cycle arrest PAI1: suppresses migration into tissues |
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What is often deleted in pancreatic cancer? |
Smad4 |
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What type of signaling, when absent, would allow uncontrolled growth of cancers? |
TGFB |
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How is MS treated? What pathway does this take advantage of? Increases & decreases what? |
Interferon therapy - through cytokine JAK/STAT signaling Increases anti-inflammatory cytokines, inhibits inflammatory cytokines |
