CaMKII protects MKP-1 from proteasome degradation in endothelial cells

Michele Ciccarelli, Maria Rosaria Rusciano, Daniela Sorriento, Maria Felicia Basilicata, Gaetano Santulli, Pietro Campiglia, Alessia Bertamino, Nicola De Luca, Bruno Trimarco, Guido Iaccarino, Maddalena Illario

Research output: Contribution to journalArticle

4 Scopus citations

Abstract

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 H3-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.

Original languageEnglish (US)
Pages (from-to)2167-2174
Number of pages8
JournalCellular Signalling
Volume26
Issue number10
DOIs
StatePublished - Oct 2014
Externally publishedYes

Keywords

  • CaMKII
  • Endothelial cell
  • Phosphatases

ASJC Scopus subject areas

  • Cell Biology

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  • Cite this

    Ciccarelli, M., Rusciano, M. R., Sorriento, D., Basilicata, M. F., Santulli, G., Campiglia, P., Bertamino, A., De Luca, N., Trimarco, B., Iaccarino, G., & Illario, M. (2014). CaMKII protects MKP-1 from proteasome degradation in endothelial cells. Cellular Signalling, 26(10), 2167-2174. https://doi.org/10.1016/j.cellsig.2014.06.009