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47 Cards in this Set
- Front
- Back
Properties of GPCRs
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7 transmembrane domains
intracellular domain extracellular domain |
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primary site of interaction of GPCR with g-protein is
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loop 3
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GPCRs respond to
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a diverse array of extracellular signals
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structural properties of G proteins
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three subunits: alpha, beta, gamma
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alpha subunit of g preotins is bound to
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GDP
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diverse combinations of alpha, beta, and gamma can cause
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diverse effects
gs, gi, gq 5 beta 11 gamma |
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specificity of g-protein is dictated by
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-different G protein families control different signaling cascades
-a given receptor can bind to multiple ligands with diff. affinities |
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conformational change in the heterodimer g-protein promotes
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nucleotide exchange which is activation
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GEF
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guanine nucleotide exchange factor
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RGS
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protein that increases rate of GTP hydrolysis to GDP
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GAP
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protein that increases GTPase activity
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effector molecules
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become activated by binding of active G protein subunits
-trigger downstream signaling effects - typically involved in the production of second messengers |
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heterologous desensitization
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PKA and PKC bind GPCR receptors with and without ligands
they can no longer interact with g-protein |
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homologous desensitization
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kinases only phosphorylate only ligand-occupied GPCRs
these recruit and bind Arr Arr bound receptor is internalized and degraded/phosphorylated |
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second messenger properties
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small, non-protein molecules
rapidly produced or mobilized readily diffusible bind efectors |
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major second messengers
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cyclic AMP
cyclic GMP IP3 Ca2+ DAG NO. |
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____converts ATP to cAMP
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Adenylate cyclase
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AC is activated by:
inhibited by: |
GalphaS
Galphai |
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an example of cAMP is______
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EPAC- a GEF for a small G protein
acts on diverse effector molecules |
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primary target of cAMP is___
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cyclic AMP dependent protein kinase (PKA)
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Structure of PKA
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2 regulatory subunits and 2 catalytic subunits
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PKA phosphorylation of GPCRs leads to
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heterologous desensitization
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PKA phosphorylates
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metabolic enzymes: inhibits gluconeogenesis
CFTR: increases transoprt of salt/water across membrane CREB: TF, now able to activate transcription of genes containing cAMP response elements GPCR: heterologous desensitization |
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Cholera Toxin
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ADP ribosylation of GalphaS
so GTP cannot be hydrolyzed to GDP and P |
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physiological results of cholera toxin
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PKA phosphorylates and activates CFTR- leads to secretion of salt into intestinal lumen followed by osmosis of water and massive diarhhea and dehydration and can even lead to death
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cGMP causes
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vasodilation, smooth muscle relaxation
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PLC activated by
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Galphaq and beta gamma subunits which are released by G alpha i
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PLC can also be activated by
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TK and small G proteins and other Galpha subunits
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function of PLC
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cleaves PIP2 to DAG and IP3
with G alphaq speeds up rxn |
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PKC in response to DAG
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binds DAG leading to partial activation and binds Ca2+ leading to full activation
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fully active PKC
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phosphorylates lots of sustrates involved in numerous pathways
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Ca2+ activates
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AC, phospholipase A2
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Ca2+ inhibits
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AC in some cases
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Ca2+ also binds
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calmodulin which controls the activity of various calmodulin-dependent kinases/phosphatases
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high concentration of Ca2+ triggers opening of
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ryanodine receptors in sarcoplasmic reticulum- causes muscle contraction
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is iNOS controlled by Ca2+
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no but NOS is regulated by Ca2+
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free Ca2+ is soaked up by
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calmodulin and other ca-binding proteins
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SERCA
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active pump: pumps Ca2+ back into sarcoplasmic/endoplasmic reticulum
-no muscle contraction iNOS is destabilized and degraded |
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cross-talk
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transduction pathways are not in solation of each other
-the activity of one cascade can affect the activity of another -this is why drugs have side effects |
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qualities of apoptosis
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programmed
physiological/pathological tightly regulated cell shrinkage membranes intact no inflammation energy required discrete DNA fragmentation |
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properties of necrosis
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accidental
pathological unregulated cell swelling membranes are destroyed inflammation energy not required randomized DNA breakdown |
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caspases are ______ to be activated
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cleaved
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IAP
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bind/inhibit caspases
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Smac/DIABLO
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inhibits IAP
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anti-apoptotic proteins
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Bcl-2
Bcl-XL |
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pro-apoptotic proteins
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multi-domain
-Bax -Bak BH3-domain only -NOXA -Bid -Bim -Bad |
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activation of multi domain proteins comes from
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activation of BH3 only domains
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