Identification of molecular determinants for protein kinase c isotype-specific functions in human leukemia cell proliferation and differentiation

Nicole R. Murray, Susan D. Walker, David J. Burns, Alan P. Fields

Research output: Contribution to journalArticle

Abstract

Protein kinase C is involved in the proliferation and differentiation of many cells types. Human erythrolenkemia (K562) cells express the α, βII and ÇPKC isotypes. Using overexpression and antisense techniques we have determined that Q PKC is involved in phorbol 12-myristate 13-acetate (PMA)-induced cytostasis while βn PKC is required for cell proliferation. To identify regions within a and βjj PKC that allow participation in these divergent pathways, we constructed chimera in which the regulatory and catalytic domains of a and βII PKC were exchanged. These PKC chimeras can be stably expressed, exhibit enzymatic properties similar to native a and βII PKC in vitro, and participate in Q and βn PKC isotype-specific signalling pathways in whole cells. Using these chimera we have demonstrated that the catalytic domains of Q and βII PKC contain determinants important for PKC isotype-selective function. These results suggest that the catalytic domain represents a poten-tial target for modulating PKC isotype activity in vivo.

Original languageEnglish (US)
Pages (from-to)A1513
JournalFASEB Journal
Volume10
Issue number6
StatePublished - Dec 1 1996

ASJC Scopus subject areas

  • Biotechnology
  • Biochemistry
  • Molecular Biology
  • Genetics

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