Role of Protein Kinase Cα in Signaling from the Histamine H1Receptor to the Nucleus
| Autor: | Stephen J. Hill, E. M. Walker, A. C. Megson |
|---|---|
| Rok vydání: | 2001 |
| Předmět: |
PRKCQ
Protein Kinase C-alpha MAP Kinase Kinase 1 Gene Expression CHO Cells Histamine H1 receptor Protein Serine-Threonine Kinases Mitogen-activated protein kinase kinase Biology chemistry.chemical_compound Histamine receptor Histamine H2 receptor Cricetinae Cyclic AMP Animals Receptors Histamine H1 Protein kinase A Protein Kinase C Protein kinase C Cell Nucleus Mitogen-Activated Protein Kinase Kinases Pharmacology Molecular biology Isoenzymes chemistry Phorbol Molecular Medicine Calcium Proto-Oncogene Proteins c-fos Signal Transduction |
| Zdroj: | Molecular Pharmacology. 59:1012-1021 |
| ISSN: | 1521-0111 0026-895X |
| DOI: | 10.1124/mol.59.5.1012 |
| Popis: | Stimulation of histamine H(1) receptors produced a marked activation of inositol phospholipid hydrolysis, intracellular calcium mobilization, and stimulation of the c-fos promoter in CHO-H1 cells expressing the H(1) receptor at a level of 3 pmol/mg protein. The latter response was determined using a luciferase-based reporter gene (pGL3). This response to histamine was not sensitive to inhibition by pertussis toxin but could be completely attenuated by the protein kinase C (PKC) inhibitor Ro-31-8220, or by 24-h pretreatment with the phorbol esters phorbol 12,13-dibutyrate or phorbol-12-myristate-13-acetate. Several isoforms of PKC can be detected in CHO-H1 cells (alpha, delta, epsilon, mu, iota, zeta) but only PKCalpha and PKCdelta were down-regulated by prolonged treatment with phorbol esters. Of the two isoforms that were down-regulated, only protein kinase Calpha was translocated to CHO-H1 cell membranes after stimulation with either histamine or phorbol esters. The PKC inhibitor Gö 6976, which inhibits PKCalpha but not PKCdelta, was also able to significantly attenuate the c-fos-luciferase response to histamine. The mitogen-activated protein kinase kinase inhibitor PD 98059 markedly inhibited the response to histamine, suggesting that the likely major target for PKCalpha was the mitogen-activated protein kinase pathway. These data suggest that the histamine H(1) receptor can signal to the nucleus via PKCalpha after activation of phospholipase Cbeta. |
| Databáze: | OpenAIRE |
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