2 Example GPCR Pathways

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[1] End result: a change in gene expression

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Extracellular signal?activates TM receptor;

Activated receptor?activates G protein;

G protein?activates adenylyl cyclase;

Activated adenylyl cyclase?makes cAMP;

cAMP causes the conformational change of Protein Kinase A (PKA)?to expose NLS;

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Kinases in GPCR paths: Ser/Thr kinases, not transmembrane proteins;

Kinases in RTK paths: Tyr Kinases and they are transmembrane proteins.

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Kinase enters the nucleus, phosphorylates a transcription factor, causing changes in gene expression.

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signaling machinery between the receptor & the TF is the same in different cells, but have different genes respond.

The message is Relayed from membrane to cytoplasm / to nucleus; a single signaling molecule is Amplified at several steps.

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[2] Liver, Muscle cells

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Adrenaline causes glycogen breakdown.

glycogen = polymerized glucose

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4 Enzymes in the path: many amplifications

Adenylyl cyclase?makes cAMP?that activates PKA,?that phosphorylates/activates Phosphorylase Kinase, which phosphorylates / activates Glycogen Phosphorylase, that breaks down glycogen into glucose (quick energy burst) - no transcription, rapid responses.

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cAMP phosphodiesterase (PDE) turns off the pathway. Caffeine inhibits cAMP PDE, so Phosphorylase Kinase?will be more active and there will be more glucose in the blood stream.