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proteins involved in Gprotein linked cAMP cascade
- H2O sol hormone + receptor (7tmd) = Gprotein(ac)
- Gp(a) splits = alpha su + (delta and gamma su)
- (alpha)GDP-> (a)GTP
- aGTP + ACi = ACa
- ACa+ ATP= cAMP
- cAMP + PKAi= PKAa
- PKAa+ CREBi= CREBa
- CREBa + CREBbp+ CREB binding element= tx
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pseudoparathyroidism
clinical- pt shows signs of PTH def: hypoCa and tetany, but PTH levels are normal
cause- PTHr mutation, abnormal Gs protein so AC is not activated enough
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Toxic thyroid nodules
- TSH from pituitary raises cAMP in thyroid causing hormone production and cell proliferation
- -problem- BENIGN tumors in thyroid overproduce hormones
- -cause- activating mutation on TSHr, Gs mutation that blocks its GTPase activity(which would deactivate)
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cholera toxin
- catalyzes covalent modification of a s/u on Gs. abolishing GTPase activity leaving it in a permanently active state. leading to increased cAMP, which causes watery diarrhea
- **also attack ZO-1 of desmosome, leading to leakage beside cells
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pertussis toxin
modifies a/s/u of Gi protein, inactivating it and leading to fluid accumulation in the lung via increased cAMP(but this time due to inavtivation of inhibitory G and not permanent activation of activating G
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DAG and IP3 as second messengers
- H2O sol hm + r = activated Gs
- Gs splits = Gs a/s/u +( b/s/u + g/s/u)
- a/s/u-GDP ==> a/s/u-GTP
- a/s/u + PLCi = PLCa
- PLCa + PIP2 = IP3 free + DAG
- IP3 to ER opens Ca ch= increase Ca IC
- Ca + DAG + PKCi = PKCa
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NMDAr
ligand gated ion channel in the brain that opens in response to glutamate
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calmodulin
Ca++ dependent enzyme activator, often activat PKs
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Ca channel blockers
inhibit VOLTAGE gated Ca channels
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ADH response in liver
Glycogen breakdown
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Thrombin (hormone)
cleaves a piece of the Thrombin-r permanently activating it
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cGMP cascade
- **no G protein involved**
- membrane bound GC are activated directly by hormones
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NO
can activate cytoplasmic GC
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ANF
- ANF + ANFr = GC (activated ANFr is GC)
- GTP + GC = cGMP
- cGMP + PKGi = PKGa (PO4ates proteins)
- **ANF causes increased Na excretion in the kidneys and relaxation of vascular SM**
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cAMP and cGMP in vascular SM
act as Ca antagonists, causing relaxation (vasodilation)
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signalling thru a GF
- GF (dimer) binds a GFr (w/ tyr kin dom) = TKa
- GFr autoPO4, where IC signalling proteins bind to PO4 an activate (allosterically), then relay signal
- -*signal proteins have an SH2 domain that bind PO4*
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insulin receptor
similar to GHr, but a IRS(insulin receptor substrate) protein binds the autoPO4 receptor, which itself then PO4s and then the SH2- containing signal proteins bind and activate
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GF signalling and activation of IP3 system
- a PLC alpha will also activate when GFr becomes PO4ed,
- PIP2----->IP3 (via PLC)
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RAS
G protein that mediated the effects of GF using mitogenic signalling cascade that activates kinases
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phosphodiestrase
- cAMP----> AMP
- *inhibited by caffeine*
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PLC gamma
- activates in response to autoPO4 GFr
- -IP3 cascade then ensues
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MAP kinase activaiton
- GF causes autoPO4 of GFr
- Ras activated by GFr
- Ras activates protein kinases
- protein kinases PO4 and activate MAP kinases
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PKB activation
- GF binds GFr and causes autoPO4
- GFr activates PI3K
- the 3-PO4 inosities activate PKB
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G protein coupled receptor deactivation
PO4 causes G protein to release and also attracts arrestin. which destines it for lysosomal degradation
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BARK
beta-r kinase that PO4 and activated beta-r and prevent G protein coupling
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