MYLK (myosin light chain kinase)

Shen, Kui; Wang, Ting; Garcia, Joe G.N.

doi:10.4267/2042/48362

Cited by 5 publications

(8 citation statements)

References 112 publications

(101 reference statements)

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“…53 kDa in average molecular weight, within a suitable range of size for practical bacterial protein expression and survived preliminary NMR trials. This protein contains three immunoglobulin C-2 type (IGc2) domains and a low-complexity region (preceding the 3rd IGc2 domain) as predicted by SMART [ 27 , 34 , 35 ] ( Fig 1 ). Subsequently, a shorter 1-264aa segment of ca.…”

Section: Resultsmentioning

confidence: 99%

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Structure–Function Analysis of the Non-Muscle Myosin Light Chain Kinase (nmMLCK) Isoform by NMR Spectroscopy and Molecular Modeling: Influence of MYLK Variants

et al. 2015

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The MYLK gene encodes the multifunctional enzyme, myosin light chain kinase (MLCK), involved in isoform-specific non-muscle and smooth muscle contraction and regulation of vascular permeability during inflammation. Three MYLK SNPs (P21H, S147P, V261A) alter the N-terminal amino acid sequence of the non-muscle isoform of MLCK (nmMLCK) and are highly associated with susceptibility to acute lung injury (ALI) and asthma, especially in individuals of African descent. To understand the functional effects of SNP associations, we examined the N-terminal segments of nmMLCK by 1H-15N heteronuclear single quantum correlation (HSQC) spectroscopy, a 2-D NMR technique, and by in silico molecular modeling. Both NMR analysis and molecular modeling indicated SNP localization to loops that connect the immunoglobulin-like domains of nmMLCK, consistent with minimal structural changes evoked by these SNPs. Molecular modeling analysis identified protein-protein interaction motifs adversely affected by these MYLK SNPs including binding by the scaffold protein 14-3-3, results confirmed by immunoprecipitation and western blot studies. These structure-function studies suggest novel mechanisms for nmMLCK regulation, which may confirm MYLK as a candidate gene in inflammatory lung disease and advance knowledge of the genetic underpinning of lung-related health disparities.

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Section: Resultsmentioning

confidence: 99%

“…211 kDa) and nmMLCK2 (ca. 203 kDa), differ by 69 amino acids within exon 11 (partially deleted in nmMLCK2, see Fig 1 ) [ 27 ], a stretch that contains the highly phosphorylated Y 464 and Y 471 , suggesting that nmMLCK splice variants are differentially regulated by Tyr phosphorylation.…”

Section: Introductionmentioning

confidence: 99%

Structure–Function Analysis of the Non-Muscle Myosin Light Chain Kinase (nmMLCK) Isoform by NMR Spectroscopy and Molecular Modeling: Influence of MYLK Variants

et al. 2015

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“…Similarly, the amino-terminal extension found in the MLCK210 isoform has six additional IgG domains and actin-binding motifs (Kamm and Stull 2001). The additional actin-binding motifs in MLCK210 allow stronger interactions with the actin cytoskeleton (Kamm and Stull 2001), while the expanded IgG domain motifs may be associated with binding to other proteins such as tubulin (Kudryashov et al 2004), macrophage migration inhibition factor (MIF) (Wadgaonkar et al 2005), cortactin (Shen et al 2012), and supervillin (Takizawa et al 2007).…”

Section: Mlck-domain Structure and Human Geneticsmentioning

confidence: 99%

“…Through these interactions, supervillin apparently modulates myosin II activation by MLCK210 and contributes to myosin II assembly during cell spreading (Takizawa et al 2007). Interaction of MLCK210 with cortactin may exert regulatory action on cortactin-Arp2/3 complex that mediates assembly of the cortical actin network in endothelial cells and controls endothelial barrier (Shen et al 2012). As demonstrated above, the interactions of MLCK210 with its protein partners may be regulated by specific posttranslational modifications introduced in a vicinity of a protein-binding interface or elsewhere.…”

Section: Mlck and Signal Transductionmentioning

confidence: 99%