Step

GDP \

ATP cAMP + PPi

FIGURE 1-36 Membrane receptor activation of adenylate cyclase by binding of a hormone to its receptor. The cell membrane is depicted, which contains on its outer surface a receptor protein for a hormone. On the inside surface of the membrane is the adenylate cyclase protein and the transducer protein G. In the resting state, GDP is bound to the a-subunit of the G protein. When a hormone binds to the receptor, a conformational change occurs (step 1). The activated receptor binds to the G protein (step 2), which activates the latter so that it releases GDP and binds GTP, causing the a-subunit and the complex of ¡3- and -y-subunits to dissociate (step 3). Free G„ subunit binds to the adenylate cyclase and activates it so that it catalyzes the synthesis of cAMP from ATP (step 4); this step may involve a conformational change in G„. When GTP is hydrolyzed to GDP, a reaction most likely catalyzed by G„ itself, G„ is no longer able to activate adenylate cyclase (step 5), and G„ and GftT reassociate. The hormone dissociates from the receptor and the system returns to its resting state. [Redrawn from Darnell, J., Lodish, H., and Baltimore, D., (1986). "Molecular and Cellular Biology", p. 692. Mol. Cell. Biol., New York: Scientific American Books, Inc., New York, with the modification indicating that the a-subunit may actually contact the receptor.]

TABLE 1-9 Intracellular Second Messengers

Second messenger

Abbreviation

Cyclic AMP

Cyclic GMP

Calcium

Diacylglycerol

Inositol 1,4,5-triphosphate cAMP

cGMP

Ca2+

0 0

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