By aligning 15 exons of PPP3CA gene with ESTs (dbEST: http://www.ncbi.nlm.nih.gov/dbEST/) and sequences of the RT-PCR products generated here, we were able to identify novel, alternatively spliced PPP3CA isoforms that can be all translated in frame. Exon 1 can be individually spliced to four different downstream exons [Figure 1(A)], generating isoforms that we term CNEX1-2, 1-3, 1-4, and 1-10 [Figure 1(B)]. Different translation initiation sites for CNEX1-2 and 1-3 create different N-terminal sequences of 6 and 19 amino acids; these are followed by the translation products of exon 3 and other exons [Figure 2(A)]. CNEX1-4 and 1-10 delete 67 and 366 amino acids, respectively. These “deletions” include part or whole the phosphatase catalytic domain [Figure 2(B)], respectively. CNEX9-11 and 13-15 skip the single exons 10 and 14, respectively. Such skipped exons delete the domains responsible for binding subunit B as well as amino acids that lie N-terminal to calcineurin's autoinhibitory domain [Figure 2(B)]. CNEX3-12 skips exon 4-11. The resultant 274 amino acid deletion removes both phosphatase catalytic and subunit B binding domains [Figure 2(B)]. More than two dozens of calcineurin
