Molecular characterization of a mammalian smooth muscle myosin light chain kinase.

Gallagher, Patricia J.; Herring, B. Paul; Griffin, Samantha; Stull, James T.

doi:10.1016/s0021-9258(18)54375-1

Cited by 135 publications

(18 citation statements)

References 58 publications

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“…MYLK2 encodes the skeletal MLCK and MYLK3 encodes a cardiac-specific MLCK [110,111]. The MYLK1 gene encodes long non-muscle isoforms (210KDa), short smooth muscle isoforms (108KDa), and telokin (21KDa) that lacks enzymatic activity [110,112,113]. In the intestinal epithelium, two long non-muscle isoforms, MLCK1 (full-length long MLCK) and MLCK2 (which lacks a single exon), are predominantly expressed, and play a critical role in modulating various cell functions [114].…”

Section: Role Of Mlck In Phosphorylation Of Mlc-2 To Regulate Intestinal Ajcmentioning

confidence: 99%

The Regulation of Intestinal Mucosal Barrier by Myosin Light Chain Kinase/Rho Kinases

Jin

Blikslager

2020

IJMS

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The intestinal epithelial apical junctional complex, which includes tight and adherens junctions, contributes to the intestinal barrier function via their role in regulating paracellular permeability. Myosin light chain II (MLC-2), has been shown to be a critical regulatory protein in altering paracellular permeability during gastrointestinal disorders. Previous studies have demonstrated that phosphorylation of MLC-2 is a biochemical marker for perijunctional actomyosin ring contraction, which increases paracellular permeability by regulating the apical junctional complex. The phosphorylation of MLC-2 is dominantly regulated by myosin light chain kinase- (MLCK-) and Rho-associated coiled-coil containing protein kinase- (ROCK-) mediated pathways. In this review, we aim to summarize the current state of knowledge regarding the role of MLCK- and ROCK-mediated pathways in the regulation of the intestinal barrier during normal homeostasis and digestive diseases. Additionally, we will also suggest potential therapeutic targeting of MLCK- and ROCK-associated pathways in gastrointestinal disorders that compromise the intestinal barrier.

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Section: Role Of Mlck In Phosphorylation Of Mlc-2 To Regulate Intestinal Ajcmentioning

confidence: 99%

The Regulation of Intestinal Mucosal Barrier by Myosin Light Chain Kinase/Rho Kinases

Jin

Blikslager

2020

IJMS

View full text Add to dashboard Cite

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“…Cells were also transfected with either a myc-tagged ERK1 or HA-tagged ERK2 reporter construct (pSR ␣ ) (Minden et al, 1995). In other experiments, COS-7 cells were transfected with 0.5 g of MEK ϩ cDNA and 1.5 g of pCMV5 vector and/or the same vector containing mutationally inactive rabbit MLCK, which was generated by oligonucleotide-directed mutagenesis as previously described and shown to lack enzyme activity even though it bound calmodulin (Gallagher et al, 1991). The mutant and wild-type MLCK calmodulin binding and kinase activity assays in COS cell lysates were performed as previously described (Herring et al, 1992;Gallagher et al, 1993).…”

Section: Transfection Of Cos-7 Cellsmentioning

confidence: 99%

Regulation of Cell Motility by Mitogen-activated Protein Kinase

Klemke

Cai

Giannini

et al. 1997

The Journal of Cell Biology

1,168

991

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Cell interaction with adhesive proteins or growth factors in the extracellular matrix initiates Ras/ mitogen-activated protein (MAP) kinase signaling. Evidence is provided that MAP kinase (ERK1 and ERK2) influences the cells' motility machinery by phosphorylating and, thereby, enhancing myosin light chain kinase (MLCK) activity leading to phosphorylation of myosin light chains (MLC). Inhibition of MAP kinase activity causes decreased MLCK function, MLC phosphorylation, and cell migration on extracellular matrix proteins. In contrast, expression of mutationally active MAP kinase kinase causes activation of MAP kinase leading to phosphorylation of MLCK and MLC and enhanced cell migration. In vitro results support these findings since ERK-phosphorylated MLCK has an increased capacity to phosphorylate MLC and shows increased sensitivity to calmodulin. Thus, we define a signaling pathway directly downstream of MAP kinase, influencing cell migration on the extracellular matrix.

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“…11 In contrast to skMLCK or cMLCK, smMLCK bears an additional C-terminal insert, and a long N-terminus that contains a fibronectin domain, two immunoglobin domains, and numerous putative phosphorylation sites. 1,6,10 The smMLCK has 1147 amino acids 12 and is also called MLCK108 based on its predicted molecular weight of 108 kDa. MLCK108 shows apparent weights ranging 125 -155 kDa, 4 compared with 77 -103 kDa for skMLCK.…”

Section: Muscle Mlck Isoformsmentioning

confidence: 99%

Myosin light chain kinase in microvascular endothelial barrier function

Shen

Rigor

Pivetti

et al. 2010

Cardiovascular Research

212

198

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Microvascular barrier dysfunction is implicated in the initiation and progression of inflammation, posttraumatic complications, sepsis, ischaemia-reperfusion injury, atherosclerosis, and diabetes. Under physiological conditions, a precise equilibrium between endothelial cell-cell adhesion and actin-myosin-based centripetal tension tightly controls the semi-permeability of microvascular barriers. Myosin light chain kinase (MLCK) plays an important role in maintaining the equilibrium by phosphorylating myosin light chain (MLC), thereby inducing actomyosin contractility and weakening endothelial cell-cell adhesion. MLCK is activated by numerous physiological factors and inflammatory or angiogenic mediators, causing vascular hyperpermeability. In this review, we discuss experimental evidence supporting the crucial role of MLCK in the hyperpermeability response to key cell signalling events during inflammation. At the cellular level, in vitro studies of cultured endothelial monolayers treated with MLCK inhibitors or transfected with specific inhibiting peptides have demonstrated that induction of endothelial MLCK activity is necessary for hyperpermeability. Ex vivo studies of live microvessels, enabled by development of the isolated, perfused venule method, support the importance of MLCK in endothelial permeability regulation in an environment that more closely resembles in vivo tissues. Finally, the role of MLCK in vascular hyperpermeability has been confirmed with in vivo studies of animal disease models and the use of transgenic MLCK210 knockout mice. These approaches provide a more complete view of the role of MLCK in vascular barrier dysfunction.

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Molecular characterization of a mammalian smooth muscle myosin light chain kinase.

Cited by 135 publications

References 58 publications

The Regulation of Intestinal Mucosal Barrier by Myosin Light Chain Kinase/Rho Kinases

The Regulation of Intestinal Mucosal Barrier by Myosin Light Chain Kinase/Rho Kinases

Regulation of Cell Motility by Mitogen-activated Protein Kinase

Myosin light chain kinase in microvascular endothelial barrier function

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