Mitogen-activated protein kinase phosphatase-1 (MKP-1) preferentially dephosphorylates p42/44MAPK but not p38MAPK in rat pinealocytes.

Authors: Price, DM  Wloka, MT  Chik, CL  Ho, AK 
Citation: Price DM, etal., J Neurochem. 2007 Jun;101(6):1685-93. Epub 2007 Apr 16.
Pubmed: (View Article at PubMed) PMID:17437549
DOI: Full-text: DOI:10.1111/j.1471-4159.2007.04557.x

We recently reported a diurnal and norepinephrine (NE) -induced expression of mitogen-activated protein kinase (MAPK) phosphatase-1 (MKP-1) in the rat pineal gland and postulated that this MKP-1 expression might impact adrenergic-regulated arylalkylamine-N-acetyltransferase (AA-NAT) activity via modulation of MAPKs. In this study, we investigated the effect of depletion of MKP-1 expression by using doxorubicin, a topoisomerase inhibitor that suppresses the expression of MKP-1 in other cell types and small interfering RNA targeted against Mkp1 in NE-stimulated pinealocytes. We found that both treatments were effective in inhibiting NE induction of MKP-1 expression. Moreover, both treatments also resulted in a prolonged activation of p42/44MAPK and an increase in AA-NAT induction by NE. In contrast, treatment of pinealocytes with PD98059, an inhibitor of MAPK kinase, reduced NE-stimulated AA-NAT activity. Interestingly, suppressing MKP-1 expression had no effect on the time profile of NE-stimulated p38MAPK activation. These results indicate that MKP-1 modulates the profile of AA-NAT activity by selectively shaping the activation profile of p42/44MAPK but not that of p38MAPK.

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CRRD ID: 7771545
Created: 2013-12-18
Species: All species
Last Modified: 2013-12-18
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RGD is funded by grant HL64541 from the National Heart, Lung, and Blood Institute on behalf of the NIH.