PROTEIN KINASE C CHIMERAS - CATALYTIC DOMAINS OF ALPHA AND BETA(II) PROTEIN KINASE C CONTAIN DETERMINANTS FOR ISOTYPE-SPECIFIC FUNCTION

摘要

Protein kinase C (PKC) is involved in the proliferation and differentiation of many cell types, In human erythroleukemia (K-562) cells, the PKC isoforms alpha and beta(I)I play distinct functional roles, alpha PKC is involved in phorbol 12-myristate 13-acetate-induced cytostasis and megakaryocytic differentiation, whereas beta(I)I PKC is required for proliferation, To identify regions within alpha and beta(I)I PKC that allow participation in these divergent pathways, we constructed chimeras in which the regulatory and catalytic domains of alpha and beta(I)I PKC were exchanged, These PKC chimeras can be stably expressed, exhibit enzymatic properties similar to native alpha and beta(I)I PKC in vitro, and participate in alpha and beta(I)I PKC isotype-specific pathways in K-562 cells. Expression of the beta/alpha PKC chimera induces cytostasis in the same manner as overexpression of wild-type alpha PKC. In contrast, the alpha/beta(I)I PKC chimera, like wild-type beta(I)I PKC, selectively translocates to the nucleus acid leads to increased phosphorylation of the nuclear envelope polypeptide lamin B in response to bryostatin-1. Therefore, the catalytic domains of alpha and beta(I)I PKC contain determinants important for alpha and beta(I)I PKC isotype function, These results suggest that the catalytic domain represents a potential target for modulating PKC isotype activity in vivo. [References: 26]