Activation of beta-isozyme of protein kinase C (PKC beta) is necessary and sufficient for phorbol ester-induced differentiation of HL-60 promyelocytes. Studies with PKC beta-defective PET mutant

Donald E Macfarlane; Lori  Manzel

doi:10.1016/S0021-9258(17)41782-0

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Activation of beta-isozyme of protein kinase C (PKC beta) is necessary and sufficient for phorbol ester-induced differentiation of HL-60 promyelocytes. Studies with PKC beta-defective PET mutant

Journal article

Open access

Peer reviewed

Activation of beta-isozyme of protein kinase C (PKC beta) is necessary and sufficient for phorbol ester-induced differentiation of HL-60 promyelocytes. Studies with PKC beta-defective PET mutant

Donald E Macfarlane and Lori Manzel

The Journal of biological chemistry, Vol.269(6), pp.4327-4331

02/11/1994

DOI: 10.1016/S0021-9258(17)41782-0

PMID: 8308000

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Abstract

12-O-Tetradecanoylphorbol-13-acetate (TPA) induces growth arrest and differentiation of a number of leukemia cell lines including HL-60 human promyelocytic leukemia. We investigated the involvement of protein kinase C (PKC) isotypes in phorbol ester-induced differentiation using the phorbol ester-tolerant PET mutant of HL-60 cells, which (in contrast to the parent phorbol ester-sensitive (wild-type) S variant of HL-60 cells) does not growth-arrest, become adherent, or undergo apoptosis when exposed to TPA (Macfarlane, D. E., Gailani, D., and Vann, K. (1988) Br. J. Haematol. 68, 291-302). In comparison to S cells, we found that proliferating PET cells markedly underexpress mRNA for PKC beta, but do express PKC alpha and PKC delta. The PKC beta-selective activator 12-deoxyphorbol 13-phenylacetate 20-acetate induces growth arrest, adherence, surface expression of CD11a, and apoptosis in S cells, but not in PET cells. Expression of PKC beta in PET cells can be restored by exposing them to dihydroxyvitamin D3, and this treatment restores the ability of subsequently added 12-deoxyphorbol 13-phenylacetate 20-acetate or TPA to induce immediate cell adherence and growth arrest of PET cells. These data led us to conclude that activation of PKC beta is both necessary and sufficient for phorbol ester-induced growth arrest and adherence in these myeloid cells.

Leukemia, Promyelocytic, Acute - pathology

Protein Kinase C - physiology

Gene Expression - drug effects

Apoptosis - drug effects

Humans

RNA, Messenger - genetics

Lymphocyte Function-Associated Antigen-1 - metabolism

Cell Adhesion - drug effects

Protein Kinase C - deficiency

Cell Differentiation - drug effects

Isoenzymes - metabolism

Calcitriol - pharmacology

Phorbol Esters - pharmacology

DNA Damage

Enzyme Activation

Tumor Cells, Cultured

In Vitro Techniques

Details

Title: Subtitle: Activation of beta-isozyme of protein kinase C (PKC beta) is necessary and sufficient for phorbol ester-induced differentiation of HL-60 promyelocytes. Studies with PKC beta-defective PET mutant
Creators: Donald E Macfarlane - Department of Medicine, Veterans Administration Hospital, Iowa City, Iowa
Lori Manzel
Resource Type: Journal article
Publication Details: The Journal of biological chemistry, Vol.269(6), pp.4327-4331
DOI: 10.1016/S0021-9258(17)41782-0
PMID: 8308000
NLM abbreviation: J Biol Chem
ISSN: 0021-9258
eISSN: 1083-351X
Language: English
Date published: 02/11/1994
Academic Unit: Hematology, Oncology, and Blood & Marrow Transplantation; Internal Medicine
Record Identifier: 9984094599202771

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