10. GPCR-adenylyl cyclase-cAMP-protein kinase A (pathway)

guanylyl cyclase

-NO receptor -stays in cytoplasm

cAMP activates protein kinase A (PKA)

-binding of PKA to cAMP dissociates inhibitory/regulatory subunit -released PKA catalytic subunits which phosphorylate target proteins -regulatory subunits localize kinase A (bind to A-kinase anchoring proteins AKAPs: bind to regulatory subunits and cell components) -PKA regulates glycogen, sugar, lipids -switch-like

turning on pathway turns it off immediately

-brief response -PKA activates cAMP phosphodiesterase -phosphodiesterase destroys cAMP/cGMP

G protein regulate production of cAMP

-cAMP acts as secondary messenger activating/binding other proteins

cAMP concentration increases rapidly

-olfactory neurons

adenylyl cyclase (adenylate cyclase)

-produces cAMP from ATP -large transmembrane protein -catalytic domain in cytosolic domain -alpha subunit of G protein activates adenylyl cylcase

PKA phosphorylates transcription factor: CREB protein

-transcription factor CREB: cAMP response element binding protein -after phosphorylated by PKA, CREB binds to CRE -phosphorylated CREB recuits CBP (CREB binding protein) which activates transcription of target genes (chromatin remodeling factor) -CREB: development of neurons, long memory, survival, organs

change in cAMP concentration can alter gene transcription

1) GPCR activates G protein 2) G protein activates adenylyl cyclase 3) increase in cAMP conc. 4) Activation of PKA 5) Phosphorylation and activation of CREB 6) CREB binds to CRE and recruits CBP to promoter 7) Transcription activation

G proteins specific for certain receptors

1) Gi = inhibitory G-protein, contains an alpha I subunit, inhibits adenylyl cyclase 2) Gs = stimulatory G-protein, contains an alpha S subunit, stimulates adenylyl cyclase 3) Gq = atypical G-protein, couples to other effector molecules

cAMP phosphodiesterase

destroys CAMP