Interferon-. alpha. selectively activates the. beta. isoform of protein kinase C through phosphatidylcholine hydrolysis
- Rockefeller Univ., New York, NY (USA)
- Syntex Research, Palo Alto, CA (USA)
The early events that occur after interferon binds to discrete cell surface receptors remain largely unknown. Human leukocyte interferon (interferon-{alpha}) rapidly increases the binding of ({sup 3}H)phorbol dibutyrate to intact HeLa cells a measure of protein kinase C activation, and induces the selective translocation of the {beta} isoform of protein kinase C from the cytosol to the particulate fraction of HeLa cells. The subcellular distribution of the {alpha} and {epsilon} isoforms is unaffected by interferon-{alpha} treatment. Activation of protein kinase C by phorbol esters mimics the inhibitory action of interferon-{alpha} on HeLa cell proliferation and down-regulation of protein kinase C blocks the induction of antiviral activity by interferon-{alpha} in HeLa cells. Increased phosphatidylcholine hydrolysis and phosphorylcholine production is accompanied by diacylglycerol production in response to interferon. However, inositol phospholipid turnover and free intracellular calcium concentration are unaffected. These results suggest that the transient increase in diacylglycerol, resulting from phosphatidylcholine hydrolysis, may selectively activate the {beta} isoform of protein kinase C. Moreover, the activation of protein kinase C is a necessary element in interferon action on cells.
- OSTI ID:
- 5464469
- Journal Information:
- Proceedings of the National Academy of Sciences of the United States of America; (United States), Vol. 87:17; ISSN 0027-8424
- Country of Publication:
- United States
- Language:
- English
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Related Subjects
INTERFERON
BIOLOGICAL EFFECTS
PHORBOL ESTERS
RADIORECEPTOR ASSAY
PHOSPHOTRANSFERASES
ENZYME INDUCTION
CELL PROLIFERATION
CHOLINE
ENZYMATIC HYDROLYSIS
HELA CELLS
LEUKOCYTES
PHOSPHOLIPIDS
TRITIUM COMPOUNDS
ALCOHOLS
AMINES
AMMONIUM COMPOUNDS
BIOLOGICAL MATERIALS
BLOOD
BLOOD CELLS
BODY FLUIDS
CARCINOGENS
CHEMICAL REACTIONS
DECOMPOSITION
DRUGS
ENZYMES
ESTERS
GENE REGULATION
GROWTH FACTORS
HYDROGEN COMPOUNDS
HYDROLYSIS
HYDROXY COMPOUNDS
ISOTOPE APPLICATIONS
LIPIDS
LIPOTROPIC FACTORS
LYMPHOKINES
LYSIS
MATERIALS
MITOGENS
ORGANIC COMPOUNDS
ORGANIC PHOSPHORUS COMPOUNDS
PHOSPHORUS-GROUP TRANSFERASES
PROTEINS
QUATERNARY COMPOUNDS
SOLVOLYSIS
TRACER TECHNIQUES
TRANSFERASES
550201* - Biochemistry- Tracer Techniques