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The second messengers cAMP and cGMP are key regulatory molecules that are involved in a wide variety of signal transduction pathways. Levels of cAMP and cGMP are regulated by their rate of synthesis by nucleotide cyclases and by their rate of hydrolysis by cyclic nucleotide phosphodiesterases (PDEs). PDEs form a superfamily of enzymes that catalyze the conversion of 3-prime, 5-prime-cyclic nucleotides to the corresponding nucleoside 5-prime-monophosphates. PDE6 is the effector enzyme in the G protein-mediated signal transduction cascade in the visual system. There are five different subunits consisting of rod and cone specific catalytic subunits: alpha' (Cone), alpha (Rod), and beta (Rod), the inhibitory subunit gamma, and subunit delta of unknown function (which likely interacts with many other proteins besides the PDE6 family). The catalytic core of the PDE6 system is comprised of alpha'/alpha' homodimers in the cone and alpha/beta heterodimers in the rod. The C-terminus of both the catalytic and inhibitory subunits is modified by methylation, myristyolation and prenylation which have been shown to be critical for proper complex assembly and membrane association.
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