PDE10A antibody

Background of PDE10A antibody

Cyclic nucleotides are important intracellular second messengers which play important role variety of signal transduction process. The cyclic nucleotides are hydrolyzed and compartmentalized by a family of enzymes called phosphodieterases. One of the many phosphodiesterases that compartmentalized and hydrolyze cAMP and cGMP in to AMP and GMP respectively are phosphodiesterase type 10. Only one member of the cAMP and cGMP-specific phosphodiesterase type-10 (PDE10) family is cloned and characterized. The PDE10A gene is expressed in at least two variant forms (PDE10A1, PDE10A2) generated by RNA splicing and or use of alternate initiation sites (1). The PDE10 gene was first cloned from fetal human lung tissue library using bioinformatics approach (2). The deduced amino acid sequence contains 779 amino acids (MW 93-95 kDa) including a putative cGMP binding domain near the N-terminal region of the protein. The catalytic portion is 16-47% identical to other PDEs and PDE10 hydrolyze cAMP and cGMP with Km 0.26 and 7.2 uM with Vmax for cGMP twice as much that for cAMP. The presence of cAMP inhibits the hydrolysis of cGMP and vise versa. PDE10A is widely expressed in putamen and caudate nucleus in the brain, thyroid and testis. Surprisingly the expression of PDE10A was also abundant in Heart (see figure 1). PDE10 subtype has at least 6 subtype variants (PDE10A2, A3, A11, A12, A13 and A14) produced by either use of alternate initiation codon or by alternate splicing. PDE10A12 is a 883 amino acid long protein with unique N-terminal sequences and a catalytic domain that is common to all PDE10A variants. Long term potentiation-associated up-regulation of some PDE10A variants is observed by differential amplification of intron-containing transcripts of the PDE10A variants.

N-terminal splice variants of PDE5A (PDE5A1 and A2) possessing unique N-terminal sequences are isolated and characterized, these variants though have similar enzymatic activities and inhibitory properties but their tissue expression patterns are vastly different. Such observations suggest that unique N-terminal transcripts of PDEs may be specifically regulated by certain transcription factors. It has been shown that PDE10A has similar splice variants with transcripts (PDE10A2 and PDE10A12) with varying length of unique N-terminal ends. The tissue distribution of PDE10A2 is confined to placenta, kidney, brain and to less extend in other tissues. The expression in fetal tissue was in brain , heart and kidney beside minor expression in other tissues (1). The PDE10A2 has a unique protein kinase A phosphorylation site (T-16), this site was not phosphorylated in PDE10A1 variant (1).