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10-28-10 Lecture 10

10-28-10 Lecture 10 - Receptor mediated signaling G-protein...

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Receptor mediated signaling G-protein coupled receptors (GPCR) • The largest superfamily of proteins in multicellular organisms • 5-10% of genome • 1000’s of receptor genes, different ligands • Sight, smell, taste, glycogen metabolism • Many diseases (blindness, hyper-thyroidism, viral induced sarcomas, high-blood pressure, schizophrenia) • Over 1/3 of pharmaceuticals work through these GPCR pathways! • Conserved mechanism • Seven trans-membrane domains
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G-protein coupled receptor signal transduction pathway Signal binds to a receptor e.g. Epinephrine to the beta adrenergic receptor Receptor binds and activates a trimeric G protein G protein e.g. alpha subunit with bound GTP activates another protein in the same membrane e.g. adenylyl cyclase Adenylyl cyclase synthesizes cAMP (a second messenger) cAMP activates a protein kinase (PKA) PKA phosphorylates a substrate –glycogen phosphorylase
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Understanding of epinephrine signaling in 1950’s by Sutherland ? 1 molecule Epinephrine (adrenaline) β -adrenergic Receptor ?
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