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

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
Pages (from-to)2167-2174
Number of pages8
JournalCellular Signalling
Volume26
Issue number10
DOIs
Publication statusPublished - 2014

Fingerprint

Calcium-Calmodulin-Dependent Protein Kinase Type 2
Proteasome Endopeptidase Complex
Endothelial Cells
Dual Specificity Phosphatase 1
Cell Proliferation
Mitogen-Activated Protein Kinase 3
Phosphoric Monoester Hydrolases
Small Interfering RNA
Signal Transduction
Nitric Oxide
Phosphotransferases
Phosphorylation
Pharmacology
Insulin
DNA

Keywords

  • CaMKII
  • Endothelial cell
  • Phosphatases

ASJC Scopus subject areas

  • Cell Biology
  • Medicine(all)

Cite this

Ciccarelli, M., Rusciano, M. R., Sorriento, D., Basilicata, M. F., Santulli, G., Campiglia, P., ... 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

CaMKII protects MKP-1 from proteasome degradation in endothelial cells. / Ciccarelli, Michele; Rusciano, Maria Rosaria; Sorriento, Daniela; Basilicata, Maria Felicia; Santulli, Gaetano; Campiglia, Pietro; Bertamino, Alessia; De Luca, Nicola; Trimarco, Bruno; Iaccarino, Guido; Illario, Maddalena.

In: Cellular Signalling, Vol. 26, No. 10, 2014, p. 2167-2174.

Research output: Contribution to journalArticle

Ciccarelli, M, Rusciano, MR, Sorriento, D, Basilicata, MF, 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, vol. 26, no. 10, pp. 2167-2174. https://doi.org/10.1016/j.cellsig.2014.06.009
Ciccarelli M, Rusciano MR, Sorriento D, Basilicata MF, Santulli G, Campiglia P et al. CaMKII protects MKP-1 from proteasome degradation in endothelial cells. Cellular Signalling. 2014;26(10):2167-2174. https://doi.org/10.1016/j.cellsig.2014.06.009
Ciccarelli, Michele ; Rusciano, Maria Rosaria ; Sorriento, Daniela ; Basilicata, Maria Felicia ; Santulli, Gaetano ; Campiglia, Pietro ; Bertamino, Alessia ; De Luca, Nicola ; Trimarco, Bruno ; Iaccarino, Guido ; Illario, Maddalena. / CaMKII protects MKP-1 from proteasome degradation in endothelial cells. In: Cellular Signalling. 2014 ; Vol. 26, No. 10. pp. 2167-2174.
@article{d47353cf566146ba9bdc6b670a474d54,
title = "CaMKII protects MKP-1 from proteasome degradation in endothelial cells",
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.",
keywords = "CaMKII, Endothelial cell, Phosphatases",
author = "Michele Ciccarelli and Rusciano, {Maria Rosaria} and Daniela Sorriento and Basilicata, {Maria Felicia} and Gaetano Santulli and Pietro Campiglia and Alessia Bertamino and {De Luca}, Nicola and Bruno Trimarco and Guido Iaccarino and Maddalena Illario",
year = "2014",
doi = "10.1016/j.cellsig.2014.06.009",
language = "English",
volume = "26",
pages = "2167--2174",
journal = "Cellular Signalling",
issn = "0898-6568",
publisher = "Elsevier Inc.",
number = "10",

}

TY - JOUR

T1 - CaMKII protects MKP-1 from proteasome degradation in endothelial cells

AU - Ciccarelli, Michele

AU - Rusciano, Maria Rosaria

AU - Sorriento, Daniela

AU - Basilicata, Maria Felicia

AU - Santulli, Gaetano

AU - Campiglia, Pietro

AU - Bertamino, Alessia

AU - De Luca, Nicola

AU - Trimarco, Bruno

AU - Iaccarino, Guido

AU - Illario, Maddalena

PY - 2014

Y1 - 2014

N2 - 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.

AB - 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.

KW - CaMKII

KW - Endothelial cell

KW - Phosphatases

UR - http://www.scopus.com/inward/record.url?scp=84904469075&partnerID=8YFLogxK

UR - http://www.scopus.com/inward/citedby.url?scp=84904469075&partnerID=8YFLogxK

U2 - 10.1016/j.cellsig.2014.06.009

DO - 10.1016/j.cellsig.2014.06.009

M3 - Article

C2 - 25007998

AN - SCOPUS:84904469075

VL - 26

SP - 2167

EP - 2174

JO - Cellular Signalling

JF - Cellular Signalling

SN - 0898-6568

IS - 10

ER -