Myosin light chain kinase in endothelium: molecular cloning and regulation.

Garcia, Joe G.N.; Lazar, Virginie; Gilbert-McClain, Lydia I.; Gallagher, Patricia J.; Verin, Alexander D.

doi:10.1165/ajrcmb.16.5.9160829

Cited by 186 publications

(193 citation statements)

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“…The unique portions of the chicken and HeLa long MLCKs (922 and 934 amino acids long, respectively), which are composed of six Ig and two DXR motifs, share only 57% identity. The HeLa long MLCK cDNA, which was amplified from a HeLa library, is 99.93% identical to the HUVEC MLCK (Garcia et al, 1997), with only four nucleotide changes. Three of these alterations are conservative, with no change in the amino acid sequence.…”

Section: Targeting Of the Long Mlck To Actin-containing Structuresmentioning

confidence: 99%

The N-terminus of the long MLCK induces a disruption in normal spindle morphology and metaphase arrest

Dulyaninova

Patskovsky

Bresnick

2004

Journal of Cell Science

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We have shown previously that only the long myosin light chain kinase (MLCK), which is the predominant MLCK isoform expressed in nonmuscle cells, localizes to the cleavage furrow. To further examine the in vivo localization of the long MLCK in HeLa cells and the mechanisms responsible for kinase targeting during the cell cycle, we examined the distribution of the endogenous kinase and constructed green fluorescent protein (GFP) fusions of long HeLa MLCK truncations. A GFP fusion containing the N-terminal IgG domain and the five DXR motifs localized to stress fibers during interphase and the cleavage furrow during mitosis. Although individual fusions of the five DXRs and IgG domain both independently localized to stress fibers, only the five DXRs demonstrated a cortical localization in mitotic cells. Thus, robust targeting of the long MLCK to the cleavage furrow required the five DXRs and additional sequences from the IgG domain. Expression of the IgG domain alone or with five DXRs increased the number of multinucleate cells tenfold, whereas expression of the five DXRs or GFP had no effect. Furthermore, expression of the IgG domain alone or with five DXRs disrupted normal spindle morphology during mitosis. Extended astral microtubules and increased bundling of kinetochore microtubules, and spindle pole fragmentation were detected in mitotic cells. These microtubule defects were associated with abnormalities in metaphase chromosome alignment and a subsequent metaphase arrest caused by activation of the spindle assembly checkpoint at the kinetochores of mono-oriented chromosomes. Together, these results suggest that MLCK has an unexpected regulatory function during mitosis.

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Section: Targeting Of the Long Mlck To Actin-containing Structuresmentioning

confidence: 99%

The N-terminus of the long MLCK induces a disruption in normal spindle morphology and metaphase arrest

Dulyaninova

Patskovsky

Bresnick

2004

Journal of Cell Science

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“…This kinase is mostly expressed in monocytes and platelets in comparison with muscular isoforms, and it is the only isoform of MLCK expressed in endothelial cells 15. This isoform (210 kDa) is, as the smooth muscle isoform (108 kDa), encoded by the mylk1 gene, although it differs both in its structure and function 16. nmMLCK phosphorylates the myosin light chain, leading to changes in cytoskeleton architecture, resulting in the retraction of the cells 17.…”

Section: Introductionmentioning

confidence: 99%

Nonmuscle Myosin Light Chain Kinase: A Key Player in Intermittent Hypoxia‐Induced Vascular Alterations

Arnaud

Bouyon

Recoquillon

et al. 2018

JAHA

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BackgroundObstructive sleep apnea is characterized by repetitive pharyngeal collapses during sleep, leading to intermittent hypoxia (IH), the main contributor of obstructive sleep apnea–related cardiovascular morbidity. In patients and rodents with obstructive sleep apnea exposed to IH, vascular inflammation and remodeling, endothelial dysfunction, and circulating inflammatory markers are linked with IH severity. The nonmuscle myosin light chain kinase (nmMLCK) isoform contributes to vascular inflammation and oxidative stress in different cardiovascular and inflammatory diseases. Thus, in the present study, we hypothesized that nmMLCK plays a key role in the IH‐induced vascular dysfunctions and inflammatory remodeling.Methods and ResultsTwelve‐week‐old nmMLCK +/+ or nmMLCK −/− mice were exposed to 14‐day IH or normoxia. IH was associated with functional alterations characterized by an elevation of arterial blood pressure and stiffness and perturbations of NO signaling. IH caused endothelial barrier dysfunction (ie, reduced transendothelial resistance in vitro) and induced vascular oxidative stress associated with an inflammatory remodeling, characterized by an increased intima‐media thickness and an increased expression and activity of inflammatory markers, such as interferon‐γ and nuclear factor‐κB, in the vascular wall. Interestingly, nmMLCK deletion prevented all IH‐induced functional and structural alterations, including the restoration of NO signaling, correction of endothelial barrier integrity, and reduction of both oxidative stress and associated inflammatory response.ConclusionsnmMLCK is a key mechanism in IH‐induced vascular oxidative stress and inflammation and both functional and structural remodeling.

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“…Ca 2ϩ /calmodulin activates myosin light chain kinase, a key enzyme in the contractile process. 17 Thrombin-induced cytoskeletal remodeling and vWF secretion appear to have a similar rapid time course. 16 Because secretion and cytoskeletal remodeling are regulated by a rise in [Ca 2ϩ ] i , there could be a mechanistic link between these 2 events, as has been suggested in several other cell types.…”

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confidence: 99%

Regulated von Willebrand Factor Secretion Is Associated With Agonist-Specific Patterns of Cytoskeletal Remodeling in Cultured Endothelial Cells

Vischer

Barth

Wollheim

2000

ATVB

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Myosin light chain kinase in endothelium: molecular cloning and regulation.

Cited by 186 publications

References 20 publications

The N-terminus of the long MLCK induces a disruption in normal spindle morphology and metaphase arrest

The N-terminus of the long MLCK induces a disruption in normal spindle morphology and metaphase arrest

Nonmuscle Myosin Light Chain Kinase: A Key Player in Intermittent Hypoxia‐Induced Vascular Alterations

Regulated von Willebrand Factor Secretion Is Associated With Agonist-Specific Patterns of Cytoskeletal Remodeling in Cultured Endothelial Cells

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