Download - Seven-Transmembrane Receptor Signaling Heterotrimeric G-proteins & Second Messenger Pathways
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Seven-Transmembrane Receptor Signaling
Heterotrimeric G-proteins & Second Messenger Pathways
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7TM Receptor Interacting with Trimeric G-Protein
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Canonical 7TM Signaling Pathway - I• Activated receptor• Binds heterotrimeric G-protein (G)
– specific ones for specific receptors
• Activated receptor is GEF– exchanges GDP for GTP on G
– G dissociates from G
• G activates/inhibits downstream transducers – adenylyl cyclases– phosphodiesterases– phospholipases
• G activates/inhibits downstream transducers– inhibition of kinases that inactivate 7TM receptors
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Canonical 7TM Signaling Pathway – II• Adenylyl cyclase
– synthesis if cAMP ([cAMP] increase 100X)– cAMP activates protein kinase A (PKA)
• PKA (S/T kinase)– regulated by RII (regulatory II) subunit
• RII subunit is binds cAMP or PKA catalytic subunit
– deregulation by cAMP allows PKA to phosphorylate numerous substrates
– PKA can enter nucleus and phosphorylate many transcriptions factors
• activates and inhibits
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Canonical 7TM Signaling Pathway – III
• Turning off the signals– RGS – regulators of G-protein signaling)
• GAPs for G subunits that stimulate GTP hydrolysis
• hydrolysis allows G
reassociation
– downstream kinasesphosphorylate 7TMreceptors
• blocks further G proteinstimulation
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Cyclic Nucleotides
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Adenylyl Cyclase
• Converts ATP to cAMP
• Stimulated by Gs
• Inhibited by Gi
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Removal of Cyclic Nucleotides
• Phosphodiesterases cut 3'-O-P bond to generate 5' nucleoside monophosphates
• cAMP AMP
• cGMP GMPPhosphodiesterase
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Cyclic Nucleotide Activated Kinases
• Protein kinases– PKA
• cAMP• cAMP binds to RII subunit • releases PKA from autoinhibition
– PKG• cGMP
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-Andrenergic Receptors
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Formation of Lipid 2nd Messengers
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Lipid Second Messengers & Targets
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Lipid 2nd Messenger Activated Protein Kinases
• Protein Kinase C Family
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Phosphoinositol Second
Messenger Signaling
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Ca2+ Second Messenger Signaling
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Odorant Receptors
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Photoreceptors
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Eicosanoids
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