GPCR Pathways

2 Example GPCR Pathways

[1] End result: a change in gene expression

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;

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

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

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

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.

[2] Liver, Muscle cells

Adrenaline causes glycogen breakdown.

glycogen = polymerized glucose

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.

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.