Unknown

Dataset Information

0

Calmodulin-dependent kinase II mediates vascular smooth muscle cell proliferation and is potentiated by extracellular signal regulated kinase.


ABSTRACT: Vascular smooth muscle cell (VSMC) proliferation contributes to vascular remodeling in atherosclerosis and hypertension. Calcium-dependent signaling through calcium/calmodulin-dependent kinase II (CaMKII) and ERK1/2 activation plays an important role in the regulation of VSMC proliferation by agents such as alpha-adrenergic receptor agonists. Nevertheless, how the CaMKII and ERK pathways interact in VSMCs has yet to be characterized. The aim of the present study was to clarify this interaction in response to alpha(1)-adrenergic receptor-mediated VSMC proliferation. We discovered that phenylephrine stimulation resulted in complex formation between CaMKII and ERK in a manner that facilitated phosphorylation of both protein kinases. To assess the effects of CaMKII/ERK association on VSMC proliferation, we inhibited endogenous CaMKII either pharmacologically or by adenoviral-mediated gene transfer of a kinase-inactive CaMKII mutant. Inhibition of CaMKII activation but not CaMKII autonomous activity significantly decreased formation of the CaMKII/ERK complex. On the contrary, the expression of constitutively active CaMKII enhanced VSMC growth and CaMKII/ERK association. In addressing the mechanism of this effect, we found that CaMKII could not directly phosphorylate ERK but instead enhanced Raf1 activation. By contrast, ERK interaction with CaMKII facilitated CaMKII phosphorylation and promoted its nuclear localization. Our results reveal a critical role for CaMKII in VSMC proliferation and imply that CaMKII facilitates assembly of the Raf/MEK/ERK complex and that ERK enhances CaMKII activation and influences its subcellular localization.

SUBMITTER: Cipolletta E 

PROVIDER: S-EPMC2875822 | BioStudies | 2010-01-01T00:00:00Z

REPOSITORIES: biostudies

Similar Datasets

2011-01-01 | S-EPMC3164514 | BioStudies
2012-01-01 | S-EPMC3408812 | BioStudies
2013-01-01 | S-EPMC3868483 | BioStudies
1000-01-01 | S-EPMC3048686 | BioStudies
2014-01-01 | S-EPMC4047873 | BioStudies
2002-01-01 | S-EPMC6758231 | BioStudies
2018-01-01 | S-EPMC5970052 | BioStudies
2018-01-01 | S-EPMC5984714 | BioStudies
2015-01-01 | S-EPMC4599535 | BioStudies
1000-01-01 | S-EPMC5541931 | BioStudies