Regulation of Vascular Smooth Muscle Migration by Mitogen-activated Protein Kinase and Calcium/Calmodulin-dependent Protein Kinase II Signaling Pathways

1998 ◽  
Vol 30 (11) ◽  
pp. 2377-2389 ◽  
Author(s):  
Martha S. Lundberg ◽  
Karen A. Curto ◽  
Claudio Bilato ◽  
Robert E. Monticone ◽  
Michael T. Crow
Keyword(s):  
Smooth Muscle ◽  
Protein Kinase ◽  
Vascular Smooth Muscle ◽  
Signaling Pathways ◽  
Mitogen Activated Protein Kinase ◽  
Dependent Protein Kinase ◽  
Calcium Calmodulin Dependent ◽  
Protein Kinase Ii ◽  
Mitogen Activated Protein ◽  
Dependent Protein

iNOS regulation by calcium/calmodulin-dependent protein kinase II in vascular smooth muscle

2007 ◽  
Vol 292 (6) ◽  
pp. H2634-H2642 ◽  
Author(s):  
Rachel J. Jones ◽  
David Jourd'heuil ◽  
John C. Salerno ◽  
Susan M. E. Smith ◽  
Harold A. Singer
Keyword(s):  
Smooth Muscle ◽  
Protein Kinase ◽  
Vascular Smooth Muscle ◽  
Resting Cells ◽  
Dependent Manner ◽  
Dependent Protein Kinase ◽  
Cytokine Induction ◽  
Calcium Calmodulin Dependent ◽  
Protein Kinase Ii ◽  
Dependent Protein

Nitric oxide synthase (NOS) expression is regulated transcriptionally in response to cytokine induction and posttranslationally by palmitoylation and trafficking into perinuclear aggresome-like structures. We investigated the effects of multifunctional calcium/calmodulin-dependent protein kinase II protein kinase (CaMKII) on inducible NOS (iNOS) trafficking in cultured rat aortic vascular smooth muscle cells (VSMCs). Immunofluorescence and confocal microscopy demonstrated colocalization of iNOS and CaMKIIδ2 with a perinuclear distribution and concentration in aggresome-like structures identified by colocalization with γ-tubulin. Furthermore, CaMKIIδ2 coimmunoprecipitated with iNOS in a CaMKII activity-dependent manner. Addition of Ca2+-mobilizing stimuli expected to activate CaMKII; a purinergic agonist (UTP) or calcium ionophore (ionomycin) caused a general redistribution of iNOS from cytosolic to membrane and nuclear fractions. Similarly, adenoviral expression of a constitutively active CaMKIIδ2 mutant altered iNOS localization, shifting iNOS from the cytosolic fraction. Suppression of CaMKIIδ2 using an adenovirus expressing a short hairpin, small interfering RNA increased nuclear iNOS localization in resting cells but inhibited ionomycin-induced translocation of iNOS to the nucleus. Following addition of these chronic and acute CaMKII modulators, there were fewer aggresome-like structures containing iNOS. All of the treatments that chronically affected CaMKII activity or expression significantly inhibited iNOS-specific activity following cytokine induction. The results suggest that CaMKIIδ2 may be an important regulator of iNOS trafficking and activity in VSMCs.

scholarly journals p38 Mitogen-activated Protein Kinase-, Calcium-Calmodulin–dependent Protein Kinase-, and Calcineurin-mediated Signaling Pathways Transcriptionally Regulate Myogenin Expression

2002 ◽  
Vol 13 (6) ◽  
pp. 1940-1952 ◽  
Author(s):  
Qing Xu ◽  
Lu Yu ◽  
Lanying Liu ◽  
Ching Fung Cheung ◽  
Xue Li ◽  
...  
Keyword(s):  
Protein Kinase ◽  
Signaling Pathways ◽  
Histone Deacetylases ◽  
Mitogen Activated Protein Kinase ◽  
Cis Elements ◽  
Dependent Protein Kinase ◽  
Calcium Calmodulin Dependent ◽  
Mitogen Activated Protein ◽  
Rd Cells ◽  
Dependent Protein

In this report, we identify myogenin as an important transcriptional target under the control of three intracellular signaling pathways, namely, the p38 mitogen-activated protein kinase- (MAPK), calcium-calmodulin–dependent protein kinase- (CaMK), and calcineurin-mediated pathways, during skeletal muscle differentiation. Three cis-elements (i.e., the E box, myocyte enhancer factor [MEF] 2, and MEF3 sites) in the proximal myogenin promoter in response to these three pathways are defined. MyoD, MEF2s, and Six proteins, the trans-activators bound to these cis-elements, are shown to be activated by these signaling pathways. Our data support a model in which all three signaling pathways act in parallel but nonredundantly to control myogenin expression. Inhibition of any one pathway will result in abolished or reduced myogenin expression and subsequent phenotypic differentiation. In addition, we demonstrate that CaMK and calcineurin fail to activate MEF2s in Rhabdomyosarcoma-derived RD cells. For CaMK, we show its activation in response to differentiation signals and its effect on the cytoplasmic translocation of histone deacetylases 5 are not compromised in RD cells, suggesting histone deacetylases 5 cytoplasmic translocation is necessary but not sufficient, and additional signal is required in conjunction with CaMK to activate MEF2 proteins.

Isoflurane Activates PKC and Ca2+-Calmodulin-dependent Protein Kinase II via  MAP Kinase Signaling in Cultured Vascular Smooth Muscle Cells

2002 ◽  
Vol 96 (1) ◽  
pp. 148-154 ◽  
Author(s):  
Li Zhong ◽  
Judy Y. Su
Keyword(s):  
Smooth Muscle ◽  
Protein Kinase ◽  
Vascular Smooth Muscle ◽  
Smooth Muscle Cells ◽  
Vascular Smooth Muscle Cells ◽  
Muscle Cells ◽  
Mitogen Activated Protein Kinase ◽  
Dependent Protein Kinase ◽  
Mitogen Activated Protein ◽  
Dependent Protein

Background Protein kinase C (PKC) and Ca(2+)-calmodulin-dependent protein kinase II (CaMKII) have been implicated in isoflurane-increased force in skinned femoral arterial strips. The extracellular signal-regulated kinases (ERK1/2) of mitogen-activated protein kinase have been shown to be target effectors of PKC and CaMKII. This study examined the role of the ERK1/2 signaling pathway in isoflurane activation of PKC and CaMKII using cultured vascular smooth muscle cells. Methods Vascular smooth muscle cells were prepared by cell migration from isolated rabbit femoral arterial segments. Growth of passage of vascular smooth muscle cells (80-90% confluence, passage 5-10) was arrested for 48 h before experiments, during which time phorbol 1,3-diaceylester treatment was used to down-regulate PKC. Cells were treated for 30 min with one of the inhibitors of mitogen-activated protein kinase kinase (PD98059), PKC (Go6976 and bisindolylmaleimide), or CaMKII (KN-93 and KN-62) at 10 microm. After administration of isoflurane, vascular smooth muscle cells were frozen rapidly, homogenized, and centrifuged. The homogenates were used for identification of phosphorylated ERK1/2 or for further centrifugation to separate the membrane from the cytosol for identification of PKC isoforms (alpha and epsilon) by Western blotting. Results Isoflurane increased ERK1/2 phosphorylation in a dose-dependent manner and reached a plateau at 10 min. PD98059 or down-regulated PKC blocked the increase of phosphorylated ERK1/2 levels by isoflurane, and bisindolylmaleimide, KN-93, or KN-62, but not by Go6976 reduced levels of phosphorylated ERK1/2. The membrane fraction of PKC epsilon but not of PKC alpha was increased by isoflurane. Conclusions ERK1/2 signaling is downstream of PKC and CaMKII activated by isoflurane in vascular smooth muscle cells.

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