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Signal Transduction
Kraus 25-28
32
Biochemistry
Graduate
08/15/2011

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Cards

Term
What is a ligand?
Definition
Molecule that binds w strong affinity to receptor.
Term
What type of receptor rcvs signals from epi, glu, serotonin, and histimine?
Definition
GPCRs
Term
Which type of receptor fxns via dimerization?
Definition
Enzyme coupled receptors
Term
What type of receptor rcvs signals from insulin, GFs?
Definition
RTK
Term
What are the subunits of a G-protein (coupled to GPCR)?
Definition
a,b,y
Term
Steps of activation--> deactivation process for G-proteins?
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.
Term
What is CREB?
Definition
Txn factor for PEPCK gene & a PKA substrate.
Term
Steps of the Gs transduction pathway?
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.
Term
How is expression of PEPCK (an enzyme of gluconeogenesis) increased?
Definition
Glucagon--> Gs--> AC--> cAMP--> PKA--> phosphorylates CREB--> P-CREB goes into nucleus & increases txn of PEPCK.
Term
Which steps in the GPCR transduction pathway are signal amplifying?
Definition
1)1 GPCR--> many G-proteins,
2)AC can catalyze many ATP-->cAMP rxns,
3)PKA can phophorylate many gene expression regulators.
Term
Which steps in the GPCR transduction pathway are potential branch points?
Definition
1)A G-protein can activate many effectors ie AC or Phospholipase C.
2)PKA & PKC can phosphorylate many diff substrates.
Term
What de-activates cAMP by converting it to AMP?
Definition
cAMP cyclo-phosphodiesterase
Term
Which G-protein inhibits AC?
Definition
Gi
Term
Steps of the Gq transduction pathway?
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.
Term
What disease is caused by a permanently activated Gs a-subunit and how?
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.
Term
How does the Pertussis toxin cause disease?
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.
Term
RTKs are involved in what types of cell processes?
Definition
Cell proliferation/differentiation, Regulation of metabolism.
Term
Mechanism of RTK fxn?
Definition
Ligand binds--> Dimerization--> Auto/Trans-phosphorylation.
Term
What does phosphorylation of RTK do?
Definition
1)In catalytic region incr kinase activity of RTK;
2)Outside catalytic region creates binding sites for signaling molecules.
Term
What 2 types of proteins contain SH2 domains and what does this domain do?
Definition
Enzymes & Adaptors (no catalytic activity but can assemble complexes of signaling proteins/enzymes);
SH2 domain recognizes & binds P-tyrosine on RTK.
Term
What is Grb2 and what domains does it contain?
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.
Term
What is Ras & how is it activated?
Definition
Small GTP binding protein;
GTP-Ras via GEF = active
GDP-Ras via GAP = inactive (GAP=GTPase activating protein)
Term
What are Raf & Erk?
Definition
Serine/Threonine kinases
Term
What is Mek?
Definition
Dual-specificity kinase
Term
Where can mutations in the MAP Kinase Cascade pathway lead to cancer?
Definition
Mutations in Ras--> all types of cancer; Mutations in Raf--> melanoma.
Term
Steps of MAP Kinase Cascade pathway?
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).
Term
Where can GPCRs and RTKs initiate the same pathway?
Definition
Gq & RTK activate PLPC (which cleaves PIP2)
Term
Which type of signal transduction is NOTCH?
Definition
Intracellular.
Term
What physiological actions is Notch involved in?
Definition
Development of nervous system, skeletal muscle, & hematopoesis.
Term
Steps of signal transduction in Notch pathway?
Definition
Delta (high-affinity ligand) on signaling cell binds Notch receptor--> NICR is cleaved & translocates to nucleus--> NICR binds other proteins to increase txn.
Term
*What type of proteins are almost always point of amplificaion?
Definition
Enzymes (ie PKA, PKC, Raf, Mek, etc)
Term
How does RTK initiate PIP2 cleavage?
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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