Term
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Definition
| Molecule that binds w strong affinity to receptor. |
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Term
| What type of receptor rcvs signals from epi, glu, serotonin, and histimine? |
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Definition
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Term
| Which type of receptor fxns via dimerization? |
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Definition
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Term
| What type of receptor rcvs signals from insulin, GFs? |
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Definition
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Term
| What are the subunits of a G-protein (coupled to GPCR)? |
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Definition
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Term
| Steps of activation--> deactivation process for G-proteins? |
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Definition
Activation: Ligand binds GPCR--> C3 loop binds a, decreasing its affinity for GDP--> a drops GDP & binds GTP--> a dissoc from by & binds effector proteins.
Deactivation: RGS binds a which increases its inherent GTPase activity--> GTP hydrolyzed to GDP+Pi--> a-GDP re-associates w by. |
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Term
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Definition
| Txn factor for PEPCK gene & a PKA substrate. |
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Term
| Steps of the Gs transduction pathway? |
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Definition
| a-subunit activates AC--> AC catalyzes ATP to cAMP--> cAMP causes PKA regulatory and catalytic subunits to dissociate which activates it--> PKA phosphorylates gene regulatory proteins. |
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Term
| How is expression of PEPCK (an enzyme of gluconeogenesis) increased? |
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Definition
| Glucagon--> Gs--> AC--> cAMP--> PKA--> phosphorylates CREB--> P-CREB goes into nucleus & increases txn of PEPCK. |
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Term
| Which steps in the GPCR transduction pathway are signal amplifying? |
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Definition
1)1 GPCR--> many G-proteins,
2)AC can catalyze many ATP-->cAMP rxns,
3)PKA can phophorylate many gene expression regulators. |
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Term
| Which steps in the GPCR transduction pathway are potential branch points? |
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Definition
1)A G-protein can activate many effectors ie AC or Phospholipase C.
2)PKA & PKC can phosphorylate many diff substrates. |
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Term
| What de-activates cAMP by converting it to AMP? |
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Definition
| cAMP cyclo-phosphodiesterase |
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Term
| Which G-protein inhibits AC? |
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Definition
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Term
| Steps of the Gq transduction pathway? |
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Definition
| a-subunit activates PLP C--> PLP C cleaves membrane PIP2 to IP3 + DAG--> IP3 diffuses away from mbrne--> opens IP3 gated Ca2+ release channels--> the increased Ca2+ activates PKC; DAG remains embedded in plasma mbrne and directly activated PKC--> PKC can phosphorylate many & diff proteins incl those regulating gene expression. |
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Term
| What disease is caused by a permanently activated Gs a-subunit and how? |
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Definition
| Cholera; toxin ribosylates a which makes it unable to hydrolyze GTP-->GDP+Pi, permanently active a-->--> permanently active PKA in intestinal epi--> PKA phosphorylates ion channels which opens them--> mass efflux of Cl- & H2O into gut. |
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Term
| How does the Pertussis toxin cause disease? |
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Definition
| Toxin ribosylates a-subunit of Gi causing Gi to be unable to bind GPCR--> Gi stuck in GDP-bound inactive state--> Gi can't inhibit AC--> prolonged inappropriate signal to cough. |
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Term
| RTKs are involved in what types of cell processes? |
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Definition
| Cell proliferation/differentiation, Regulation of metabolism. |
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Term
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Definition
| Ligand binds--> Dimerization--> Auto/Trans-phosphorylation. |
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Term
| What does phosphorylation of RTK do? |
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Definition
1)In catalytic region incr kinase activity of RTK;
2)Outside catalytic region creates binding sites for signaling molecules. |
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Term
| What 2 types of proteins contain SH2 domains and what does this domain do? |
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Definition
Enzymes & Adaptors (no catalytic activity but can assemble complexes of signaling proteins/enzymes);
SH2 domain recognizes & binds P-tyrosine on RTK. |
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Term
| What is Grb2 and what domains does it contain? |
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Definition
| GF Receptor Binding 2; Has 2 SH2 domains which bind to P-tyrosine on RTK & 1 SH3 domain which binds proline-rich seqs in other proteins ie SOS which is GEF for Ras. |
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Term
| What is Ras & how is it activated? |
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Definition
Small GTP binding protein;
GTP-Ras via GEF = active
GDP-Ras via GAP = inactive (GAP=GTPase activating protein) |
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Term
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Definition
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Term
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Definition
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Term
| Where can mutations in the MAP Kinase Cascade pathway lead to cancer? |
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Definition
| Mutations in Ras--> all types of cancer; Mutations in Raf--> melanoma. |
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Term
| Steps of MAP Kinase Cascade pathway? |
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Definition
| Grb2's SH2 domain binds to P-tyrosine--> SOS (which is constituitively bound to Grb2's SH3 domain) act as GEF for Ras--> Ras binds GTP becoming active--> Ras binds to Raf causing Raf to be P by kinases--> active Raf P MEK--> MEK P Erk (in 2 places)--> Erk P effector proteins (incl txn factors). |
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Term
| Where can GPCRs and RTKs initiate the same pathway? |
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Definition
| Gq & RTK activate PLPC (which cleaves PIP2) |
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Term
| Which type of signal transduction is NOTCH? |
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Definition
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Term
| What physiological actions is Notch involved in? |
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Definition
| Development of nervous system, skeletal muscle, & hematopoesis. |
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Term
| Steps of signal transduction in Notch pathway? |
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Definition
| Delta (high-affinity ligand) on signaling cell binds Notch receptor--> NICR is cleaved & translocates to nucleus--> NICR binds other proteins to increase txn. |
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Term
| *What type of proteins are almost always point of amplificaion? |
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Definition
| Enzymes (ie PKA, PKC, Raf, Mek, etc) |
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Term
| How does RTK initiate PIP2 cleavage? |
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Definition
| Phospholipase C's SH2 domain binds P-tyrosine--> brings it closer to PIP2 (on mbrne)-->PLP C cleaves PIP2 to IP3 + DAG. |
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