Opposing regulatory effects of protein kinase C on the cAMP cascade in human HL-60 promyelocytic leukemia cells
SCIE
SCOPUS
- Title
- Opposing regulatory effects of protein kinase C on the cAMP cascade in human HL-60 promyelocytic leukemia cells
- Authors
- Byung-Chang, S; Se-Young, C; Jang-Soo, C; Kyong-Tai, K
- Date Issued
- 1998-07-17
- Publisher
- ELSEVIER SCIENCE BV
- Abstract
- The functional role of protein kinase C in the cAMP signaling cascade was investigated in human promyelocytic leukemia (HL-60) cells. Protein kinase C activation after short exposure to 100 nM phorbol 12-myristate 13-acetate (PMA) increased the intracellular cAMP level up to 3- to 5-fold after 30 min. Such enhancement was almost completely blocked by the selective protein kinase C inhibitor bisindolylmaleimide (GF 109203X). In addition, PMA, but not 4-alpha-PMA, synergistically elevated cAMP levels when adenylyl cyclase was activated directly by forskolin or indirectly by G protein activation after cholera toxin treatment or guanosine 5'-O-(3-thiotriphosphate) (GTP gamma S) treatment in digitonin-permeabilized cells. The results indicate that protein kinase C directly increases adenylyl cyclase activity and synergistically enhances it, when it is simultaneously activated otherwise. On the other hand, a 10-min treatment with PMA cut the cAMP accumulation induced by histamine, prostaglandin E-2, or isoproterenol by 50-70%. However, the binding affinity and total binding of [H-3]histamine to membrane receptors was not effected by PMA, suggesting that the site of protein kinase C's action is not at the receptor level. Western blot analysis of protein kinase C isozymes revealed that PMA (100 nM) caused translocation of cytosolic protein kinase C such as alpha, beta and epsilon to the particulate/membrane fraction. Treatment with a lower concentration of PMA (10 nM) translocated the protein kinase C-epsilon within 2 min, while it had little effect on the translocation of protein kinase C-alpha and -beta up to 20 min. However, simultaneous treatment with 10 nM PMA plus histamine for 5 min significantly inhibited the histamine-mediated cAMP generation indicating that the protein kinase C-epsilon could be involved in the inhibition of receptor-mediated cAMP generation. Taken together, we conclude that PMA, through the activation of protein kinase C, has two opposite effects on the cAMP signaling cascade in HL-60 cells: a direct activation of adenylyl cyclase and an inhibition of receptor-mediated signal transduction. (C) 1998 Elsevier Science B.V. All rights reserved.
- Keywords
- HL-60 promyelocytic leukemia cell; adenylyl cyclase; histamine; protein kinase C; phorbol 12-myristate 13-acetate; NEUROBLASTOMA SK-N-BE(2)C CELLS; ADENYLATE-CYCLASE ACTIVITY; PHORBOL-MYRISTATE ACETATE; SIGNAL-TRANSDUCTION; MOLECULAR-CLONING; HUMAN NEUTROPHILS; DOWN-REGULATION; RECEPTOR; ESTER; STIMULATION
- URI
- https://oasis.postech.ac.kr/handle/2014.oak/20703
- DOI
- 10.1016/S0014-2999(98)00387-2
- ISSN
- 0014-2999
- Article Type
- Article
- Citation
- EUROPEAN JOURNAL OF PHARMACOLOGY, vol. 353, no. 1, page. 105 - 115, 1998-07-17
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