Protein kinase C chimeras: Catalytic domains of α and β(II) protein kinase C contain determinants for isotype-specific function

S. D. Walker, N. R. Murray, D. J. Burns, A. P. Fields

Research output: Contribution to journalArticle

38 Scopus citations

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 β(II) play distinct functional roles. α PKC is involved in phorbol 12-myristate 13-acetate-induced cytostasis and megakaryocytic differentiation, whereas β(II) PKC is required for proliferation. To identify regions within α and β(II) PKC that allow participation in these divergent pathways, we constructed chimeras in which the regulatory and catalytic domains of a and β(II) PKC were exchanged. These PKC chimeras can be stably expressed, exhibit enzymatic properties similar to native α and β(II) PKC in vitro, and participate in α and β(II) 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/β(II) PKC chimera, like wild-type β(II) PKC, selectively translocates to the nucleus and leads to increased phosphorylation of the nuclear envelope polypeptide lamin B in response to bryostatin-1. Therefore, the catalytic domains of α and β(II) PKC contain determinants important for α and β(II) PKC isotype function. These results suggest that the catalytic domain represents a potential target for modulating PKC isotype activity in vivo.

Original languageEnglish (US)
Pages (from-to)9156-9160
Number of pages5
JournalProceedings of the National Academy of Sciences of the United States of America
Volume92
Issue number20
DOIs
StatePublished - Oct 12 1995

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