CaMKII protects MKP-1 from proteasome degradation in endothelial cells.

Authors:
Michele Ciccarelli
Michele Ciccarelli
University of Salerno
Fisciano | Italy
Maria Rosaria Rusciano
Maria Rosaria Rusciano
University of Naples Federico II
Italy
Daniela Sorriento
Daniela Sorriento
Department of Clinical Medicine
Italy
Maria Felicia Basilicata
Maria Felicia Basilicata
"Federico II" University of Naples
Italy
Gaetano Santulli
Gaetano Santulli
Federico II University of Naples
Italy
Pietro Campiglia
Pietro Campiglia
University of Salerno
Alessia Bertamino
Alessia Bertamino
University of Naples Federico II
Italy

Cell Signal 2014 Oct 5;26(10):2167-74. Epub 2014 Jul 5.

Department of Translational Science, "Federico II" University of Naples, Italy.

CaMKs are a widely distributed family of kinases with multiple and often cell specific effects on intracellular signal transduction pathway. In endothelial cells, it has been recognized a role for CamKII in several pathways such as eNOS activation and nitric oxide production. It is not clear though, whether CaMKII interfere with other endothelial cell functions such as ERK activation and cell proliferation. We explored this issue in primary cultured rat endothelial cells and we evaluated the effect on endothelial cell proliferation and DNA synthesis. CaMKII inhibition through Cantide, conducted into the cell through Antoennapedia (ANT-CN), showed positive effects on proliferation and H(3)-thimdine incorporation similar to insulin stimulation. Accordingly, both CaMKII pharmacological inhibition and silencing through shRNA produced activation of the p44/42 MAPK. These observations leaded to the hypothesis that CamKII could regulate p44/p42 by interfering with specific ERK phosphatases. Indeed, we found that CaMKII interacts and protect the dual specific phosphatase MKP-1 from proteasome mediated degradation while this complex is disrupted by CaMKII inhibitors. This study reveals that CaMKII, besides phosphorylation through the known ras-raf-mek pathway, can regulate also dephosphorylation of p44/p42 by modulation of MKP-1 level. This novel finding opens to a novel scenario in regulation of endothelial cell functions.

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Source
http://dx.doi.org/10.1016/j.cellsig.2014.06.009DOI Listing
October 2014
15 Reads
1 Citation
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