Selective regulation of expression of protein kinase C β isoenzymes occurs via alternative splicing

The mechanisms involved in regulating the selective expression of protein kinase C (PKC) isoenzymes are poorly understood. Two human B lymphoblastoid cell lines, IM-9 and BJA-B, exhibited differential expression of the two alternatively spliced products of the PKC β gene, PKC βI and βII. The IM-9 cell line expressed 3-4-fold more PKC βII protein than the BJA-B cell line, whereas the BJA-B cell line expressed 2-3-fold more PKC βI protein. This differential expression was found to be regulated at the mRNA level. Comparison of PKC βI and βII messages in poly(A)⁺ mRNA and total cellular RNA revealed that selective polyadenylation was not involved. The messages for PKC βI and βII had comparable half-lives in both cell lines, ruling out differential message stability. In addition, similar ratios of PKC βI and βII messages in cytosolic and nuclear fractions suggested that differential mRNA transport was not involved. In the IM-9 cell line, the predominance of mature PKC βII message as well as that of a larger message spliced to PKC βII provided evidence that the differential expression of PKC βII was regulated at the level of mRNA splicing. In the BJA-B cell line, equal amounts of mature PKC βI and βII message and the absence of the larger message suggested that the splicing of the PKC β gene product can be regulated to produce altered ratios of PKC βI and βII. Implications of these studies on the differential expression of PKC isoenzymes and their roles in biology are discussed.