Novel protein kinase C δ isoform insensitive to caspase-3

Protein kinase C delta (PKC delta) plays a key regulatory role in a variety of cellular functions, including apoptosis, as well as cell growth and differentiation. We previously reported that apoptosis was induced by pretreatment with 1-(5-isoquinolinesulfonyl)-2-methylpiperazine (H-7), an inhibitor of PKC, in mouse thymocytes. In the present study, we showed that a novel PKC delta isoform (PKC delta II) was transiently expressed when thymocytes were pretreated with H-7. The analysis of the cDNA encoding PKC delta II indicated that a 78 bp fragment was inserted into the caspase-3 sensitive site of the original PKC delta (PKC deltaI), presumably by alternative splicing. The PKC delta II expressed in COS-1 cells was one product with a molecular mass of 81 kDa and with kinase activity similar to that of PKC deltaI. The expressed PKC deltaI protein (78 kDa) was in part cleaved into a 38 kDa fragment in vivo and in vitro, but the PKC delta II protein was not. Cleavage of the PKC deltaI protein was inhibited by a specific inhibitor of caspase-3, indicating that PKC delta II is insensitive to caspase-3. The PKC delta II was highly expressed in the testis and ovary, and at a lower level in the thymocytes, brain and kidney, whereas PKC delta II was detected in most tissues, suggesting that the function of PKC delta II is different from that of PKC delta II.