Myosin light chain kinase (210 kDa) is a potential cytoskeleton integrator through its unique N-terminal domain

Kudryashov, Dmitri S.; Степанова, О. В.; Vilitkevich, E. L.; Nikonenko, Tatyana A; Nadezhdina, E. S.; Shanina, N. A.; Lukas, Thomas J.; Eldik, Linda J. Van; Watterson, D. Martin; Shirinsky, Vladimir P.

doi:10.1016/j.yexcr.2004.04.025

Cited by 36 publications

(38 citation statements)

References 35 publications

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“…It is conceivable that the same could also take place for the microtubules binding assay. In fact, the pellets were formed even when no F-actin was added to the reaction as shown in Figure 6 A of their paper [36]. In addition, we failed to detect bound 2Ig peptide in tubulin pellets under our experimental condition (data not shown).…”

Section: Over-expression Of 2ig Increases Spike-like Filopodia Formationmentioning

confidence: 64%

“…While we were completing the binding assay for this study, Kudryashov et al reported that the N-terminus of long MLCK was able to bind to both F-actin and microtubules, and they proposed that long MLCK might be a potential cytoskeleton integrator through its unique N-terminal domain [36]. Surprisingly, the KD of N-terminal peptide for F-actin binding in their report was estimated to be 7.2 µM and Bmax was over 1.5 mol/mol of actin.…”

Section: Over-expression Of 2ig Increases Spike-like Filopodia Formationmentioning

confidence: 93%

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Microfilament-binding properties of N-terminal extension of the isoform of smooth muscle long myosin light chain kinase

Yang

Chen

et al. 2006

Cell Res

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Section: Over-expression Of 2ig Increases Spike-like Filopodia Formationmentioning

confidence: 64%

Section: Over-expression Of 2ig Increases Spike-like Filopodia Formationmentioning

confidence: 93%

Microfilament-binding properties of N-terminal extension of the isoform of smooth muscle long myosin light chain kinase

Yang

Chen

et al. 2006

Cell Res

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“…In addition to its catalytic kinase domain, evidence supports that MLCK210 is able to interact in the cell through specific binding with other proteins, like actin-cytoskeleton, via its NH 2 -terminal extension (16). Hence the effects related to the deletion of MLCK210 might be the consequence of either the absence of its kinase activity or of the loss of structural binding with protein partners.…”

Section: Discussionmentioning

confidence: 99%

“…This noncatalytic domain of MLCK is distinct from the kinase domain. Its role as a cellular organizer, providing integration among diverse cytoskeletal proteins, has been confirmed recently (16).…”

mentioning

confidence: 92%

Deletion of MLCK210 induces subtle changes in vascular reactivity but does not affect cardiac function

Ohlmann

Tesse²,

Loichot³

et al. 2005

American Journal of Physiology-Heart and Circulatory Physiology

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plays a key role in the regulation of actomyosin contraction in a large variety of cells. Two isoforms have been described: a short isoform, widely expressed in smooth muscle cells; and a long isoform (MLCK210), mainly localized in the endothelium. This study investigated the consequences on different cardiovascular parameters of MLCK210 gene deletion using MLCK210 knockout mice and of pharmacological inhibition of the kinase using a specific MLCK inhibitor. Deletion of MLCK210 did not affect systolic blood pressure and heart rate or echocardiographic measurements. Electrocardiographic analysis showed neither atrionor intraventricular conduction or repolarization defects. Ex vivo responses of aortic rings to vasoconstrictor and vasodilator agonists were not modified in MLCK210 null mice. However, deletion of MLCK210 attenuated shear stress-induced dilation and produced changes in the balance of endothelial-relaxing factors of small mesenteric arteries (SMA). In particular, a reduced flow-mediated NOdependent dilation was observed. However, it was partially compensated by enhanced indomethacin-sensitive dilation. No significant changes were detected in the endothelium-derived hyperpolarizing component of the vasodilator response. The above effects of MLCK210 gene deletion were confirmed in SMA from wild-type mice by the use of the MLCK enzymatic inhibitor MMZ-10 -057. In summary, deletion of MLCK210 was not associated with abnormalities of main in vivo cardiovascular parameters in mice. This study demonstrates a role for MLCK210 in the regulation of flow-dependent dilation in SMA. myosin light chain kinase 210; knockout mice; echocardiography; endothelium; vascular reactivity; shear stress MYOSIN LIGHT CHAIN KINASES (MLCK) are Ca 2ϩ

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“…A major distinguishing feature is the 922 amino acids N-terminal stretch unique to nmMLCK1, which exhibits distinct cellular functions through unique interactions with other contractile proteins. [ 8 ] and [ 9 ] Despite the uniqueness of the nmMLCK N-terminus, information is limited regarding the tissue distribution or physiologic roles of the splice variants that use the nmMLCK ATG. Northern and reverse transcription-polymerase chain reaction (RT-PCR) data 6 suggest that splice variant 2 (nmMLCK2) is the most abundant isoform in many tissues, including the endothelium.…”

Section: Translational Significancementioning

confidence: 99%

A transgenic mouse with vascular endothelial over-expression of the non-muscle myosin light chain kinase-2 isoform is susceptible to inflammatory lung injury: role of sexual dimorphism and age

Moitra

Evenoski

Sammani

et al. 2008

Translational Research

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We have generated genetically engineered mice that are uniquely susceptible to lipopolysaccharide (LPS)-induced and mechanical ventilation-induced lung injury in a sex-specific and age-specific manner. These mice express a nonmuscle isoform of the myosin light chain kinase gene (nmMLCK2) targeted to the endothelium. Homozygous mice have significantly reduced fecundity and litter survival until weaning, and they are initially growth delayed but eventually exceed the size of wildtype littermates. Mice at all ages show increased protein transport across the lung barrier; however, the phenotype is most discernible in 8-12-week-old male mice. When subjected to a clinically relevant LPS-induced lung injury model, 8-12-week-old young females and 30-36-week-old males seem to be the most significantly injured group. In contrast, 30-36-week-old males remain the most significantly injured group when mechanically ventilated at high tidal volumes, which is a clinically relevant model of mechanical stress lung injury. These data reveal that nmMLCK2 overexpression in the endothelium exacerbates lung injury in vivo in a sexually dimorphic and age-dependent manner.Actin microfilaments generate force by virtue of their ability to contract away from their site of attachment to the plasma membrane, and they do so via traction of the myosin light chain head groups attached to actin filaments by cross-bridges. The cross-bridge pulling action of myosin involves a conformational change in the molecule initiated by energetic phosphorylation of Ser19 on the myosin light chains. 1 The key enzyme involved in this phosphorylation event is myosin light chain kinase (MLCK), which exists in different tissues, and it may be characterized broadly as skeletal/cardiac, smooth muscle, and nonmuscle myosin light chain kinase (nmMLCK) isoforms. Although biochemical evidence for the existence of a Ca 2+ /calmodulin-dependent nonmuscle isoform in cultured endothelial cell (EC) was suggested earlier, [ 2 ] and [ 3 ] the controversy as to whether this enzymatic activity is identical to the 110-kDa protein found abundantly in smooth muscle preparations was resolved when we provided conclusive proof of a larger MLCK protein isoform (210 kDa) by cloning the gene (MYLK) from a human EC-derived cDNA library. 4 The gene was subsequently mapped to chromosome 3q21. 5

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Myosin light chain kinase (210 kDa) is a potential cytoskeleton integrator through its unique N-terminal domain

Cited by 36 publications

References 35 publications

Microfilament-binding properties of N-terminal extension of the isoform of smooth muscle long myosin light chain kinase

Microfilament-binding properties of N-terminal extension of the isoform of smooth muscle long myosin light chain kinase

Deletion of MLCK210 induces subtle changes in vascular reactivity but does not affect cardiac function

A transgenic mouse with vascular endothelial over-expression of the non-muscle myosin light chain kinase-2 isoform is susceptible to inflammatory lung injury: role of sexual dimorphism and age

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