Adenylyl cyclase signaling

The hormonal stimulation of adenylyl cyclase is effected by a transmembrane signaling pathway consisting of three components, all membrane-associated. Binding of hormone to the external surface of a hormone receptor causes a conformational change in this transmembrane protein, which in turn stimulates a GTP-binding protein (abbreviated G protein). G proteins are heterotrimeric proteins consisting of a- (45-47 kD), /3- (35 kD), and y- (7-9 kD) subunits. The a-subunit binds GDP or GTP and has an intrinsic, slow... 

Linder JU, Schultz JOB (2003) The Class III adenylyl cyclases multi-purpose signalling modules. Cell Signal 15 1081-1089... 

Adenylyl Cyclases Guanylyl Cyclases Transmembrane Signalling Cyclic Adenosine Monophosphate Cyclic Guanosine Monophosphate Cyclic Nucleotide-gated Channels Phosphodiesterases... 

Functionally, the Dl-like receptors (Dl, D5) are coupled to the G protein Gas and thus can stimulate adenylyl cyclase. The D2-like receptors (D2, D3, and D4) couple to pertussis toxin sensitive G proteins (Gai/0), and consequently inhibit adenylyl cyclase activity. While the Dl-like receptors almost exclusively signal through Gas-mediated activation of adenylyl cyclase, the D2-like receptors have been reported to modulate the activity of a plethora of signaling molecules and pathways. Many of these actions are mediated through the G(3y subunit. Some of these molecules and pathways include the calcium channels, potassium channels, sodium-hydrogen exchanger, arachidonic acid release, and mitogen-activated protein kinase pathways. 

The majority of GPCRs couple to three families of G protein alpha subunits which differ in their ability to activate three distinct primary signaling cascades. The stimulatory G-protein Gas, positively regulates the activity of adenylyl cyclase causing an increase of intracellular cAMP levels as second messenger. In... 

Clark MJ, Harrison C, Zhong H, et al Endogenous RGS protein action modulates mu-opioid signaling through Galphao effects on adenylyl cyclase, extracellular signal-regulated kinases, and intracellular calcium pathways. J Biol Chem 278 9418-9425, 2003... 

Berghard A. and Buck L.B. (1996). Sensory transduction in vomeronasal neurons evidence for G-alpha-o, G-alpha-i2, and adenylyl cyclase II as major components of a pheromone signaling cascade. J Neurosci 16, 909-918. 

Rossler P., Kroner C.K.J., Lobel D., Breer H., et al. (2000). Cyclic adenosine monophosphate signaling in the rat vomeronasal organ role of an adenylyl cyclase type VI. Chem Senses 25, 313-322. 

Tsu et al. [57] have reported that Gz can reconstitute 8 receptor coupling to adenylyl cyclase in HEK 293 cells after pertussis toxin treatment and studies by Law and Reisine [73] have shown that Gz can physically associate with the cloned 8 receptor. Tsu et al. [57] have also shown that Gz can couple the cloned 8 receptor to phospholipase C, providing a potential dual role of this pertussis toxin-insensitive G protein in 8 receptor signaling. 

Lustig KD, Conklin BR, Herzmark P et al. Type II adenylyl cyclase integrates coincident signals from GS, Gi and Gq. J Biol Chem 1993 268 13900-13905. 

Cyclic nucleotides are made in response to receptor activation. The receptor activates a G-protein that, in turn, activates adenylyl cyclase to make the cyclic nucleotide. To complete the signaling, the increase in cAMP concentration activates a specific protein kinase (serine/threo-nine), cAMP-dependent protein kinase (A kinase) (Fig. 9-7). To turn off the signaling pathway, the cyclic nucleotides are destroyed by enzymes called phosphodiesterases. These cleave cAMP to AMP. 

Dopamine receptors are found primarily in brain, although they also exist in kidney [33]. Two subtypes of dopamine receptor were initially identified based primarily on differences in their drug specificities and signaling mechanisms. D receptors were found to stimulate adenylyl cyclase activity, while D2 receptors inhibited this enzyme (Fig. 12-6). Subsequently, multiple Dr and D2-like receptors were identified by molecular cloning (Table 12-3) [33], All dopamine receptor subtypes are... 

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