Protein kinase C chimeras: Catalytic domains of α and βII protein kinase C contain determinants for isotype-specific function

Abstract

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