Activation of distinct protein kinase C isozymes by phorbol esters: Correlation with induction of interleukin 1. beta. gene expression

Journal Article · Tue Apr 18 04:00:00 EDT 1989 · Biochemistry; (USA)

DOI:https://doi.org/10.1021/bi00434a063· OSTI ID:5668138

Strulovici, B; Daniel-Issakani, S; Oto, E; Nestor, J Jr; Chan, H; Tsou, A P ^[1]

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1. Syntex Research, Palo Alto, CA (USA)

Treatment of human promyelocytic leukemia cells U937 with phorbol 12-myristate 13-acetate (TPA) induces them to differentiate into monocytic cells. Here the authors investigated the effects of TPA on interleukin 1 gene expression and the possible role of protein kinase C (PKC) in this process. Addition of TPA to serum-starved U937 cells induced the expression of the interleukin 1{beta} (IL-1{beta}) gene. This effect was apparent as early as 2 h and peaked at 24 h in the presence of 5 {times} 10{sup {minus}8} M TPA. To determine the protein kinase C isozymes present in the control and TPA treated U937 cells, they prepared antipeptide antibodies that specifically recognize the {alpha}, {beta}, and {gamma} isoforms of protein kinase C in rat brain cytosol and U937 cell extracts. Upon TPA treatment, there was a time-dependent translocation (maximum 1 h) of PKC {alpha} to a particulate compartment, followed by its gradual disappearance, with no concomitant rise in the cytosolic form. PKC {beta} remained cytosolic during TPA treatment, while PKC {gamma} appeared at 6 h and continued to increase in abundance by 24 h, mostly in particulate form. Exposure of {sup 32}PO{sub 4}-labeled cells to TPA for 30 min enhanced the phosphorylation of several major substrates. Exposure of U937 cells to diC{sub 8} failed to induce PKC {alpha} translocation. The data suggest a potential role for PKC {alpha} mediated phosphorylation of substrates in the initial events leading to TPA-induced differentiation of a promonocytic cell to a monocyte/macrophage.

• OSTI ID: 5668138
• Journal Information: Biochemistry; (USA), Journal Name: Biochemistry; (USA) Vol. 28:8; ISSN 0006-2960; ISSN BICHA
• Country of Publication: United States
• Language: English

Related Subjects

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59 BASIC BIOLOGICAL SCIENCES
63 RADIATION, THERMAL, AND OTHER ENVIRON. POLLUTANT EFFECTS ON LIVING ORGS. AND BIOL. MAT.
ANIMAL CELLS
ANIMALS
BETA DECAY RADIOISOTOPES
BETA-MINUS DECAY RADIOISOTOPES
BIOLOGICAL EFFECTS
BODY
BRAIN
CARCINOGENS
CELL DIFFERENTIATION
CENTRAL NERVOUS SYSTEM
CHEMICAL REACTIONS
DAYS LIVING RADIOISOTOPES
DOSE-RESPONSE RELATIONSHIPS
ELECTROPHORESIS
ENZYMES
ESTERS
HYBRIDIZATION
HYDROGEN COMPOUNDS
ISOENZYMES
ISOTOPES
LIGHT NUCLEI
MAMMALS
MAN
NERVOUS SYSTEM
NUCLEI
ODD-ODD NUCLEI
ORGANIC COMPOUNDS
ORGANS
PHORBOL ESTERS
PHOSPHORUS 32
PHOSPHORUS ISOTOPES
PHOSPHORUS-GROUP TRANSFERASES
PHOSPHORYLATION
PHOSPHOTRANSFERASES
PRIMATES
RADIOISOTOPES
RATS
RODENTS
SUBSTRATES
TRANSFERASES
TRITIUM COMPOUNDS
TUMOR CELLS
VERTEBRATES