Role of protein turnover in the activation of p38 mitogen-activated protein kinase in rat pinealocytes
In: Biochemical pharmacology, Jg. 70 (2005), Heft 12, S. 1840-1850
academicJournal
- print, 40 ref
Zugriff:
Differences in the time profiles of activation between p38MAPK and p42/44MAPK by norepinephrine (NE) in rat pinealocytes suggest involvement of mechanisms other than the phosphorylation cascades in their activation. In the present study we investigated whether protein turnover played a role in regulating p38MAPK activation in the rat pineal gland. NE stimulation caused an increase in MAPK kinase3/6 (MKK 3/6) and p38MAPK phosphorylation that occurred in the absence of changes in the mRNA or protein levels of p38MAPK or MKK3/6. The stimulatory effect of NE on phosphorylated MKK3/6 and p38MAPK, but not phosphorylated p42/44MAPK, was blocked by treatment with actinomycin or cycloheximide, indicating a requirement of transcription and translation in activation of the p38MAPK but not the p42/44MAPK pathway. Moreover, inhibition of proteasomes by clasto-lactacystin β-lactone or Z-Leu-Leu-Leu-CHO (MG132) selectively increased basal and NE-stimulated phosphorylated MKK3/6 and p38MAPK levels without affecting the mRNA or protein levels of MKK3 or p38MAPK. In contrast, the effect of proteasomal inhibition on NE-stimulated p42/44MAPK phosphorylation was inhibitory. Treatment with MG 132 also reduced the decline in the phosphorylated levels of NE-stimulated MKK3/6 and p38MAPK that normally follows p-adrenergic blockade. Together, our results indicate that p38MAPK but not p42/44MAPK activation in the rat pineal gland is tightly coupled to protein synthesis and degradation. The synthesis of an activator upstream of MKK3/6 is required for the NE-activation of p38MAPK.
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Role of protein turnover in the activation of p38 mitogen-activated protein kinase in rat pinealocytes
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Autor/in / Beteiligte Person: | HO, A. K ; MCNEIL, L ; TERRIFF, D ; PRICE, D. M ; CHIK, C. L |
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Zeitschrift: | Biochemical pharmacology, Jg. 70 (2005), Heft 12, S. 1840-1850 |
Veröffentlichung: | New York, NY: Elsevier Science, 2005 |
Medientyp: | academicJournal |
Umfang: | print, 40 ref |
ISSN: | 0006-2952 (print) |
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