Disease relevance of MYL9

• The LC20 mAb was used to affinity purify the colon cancer OSN as well as a cross-reactive normal protein from the urine of colon cancer patients and healthy donors, respectively [1].
• Helicobacter pylori strain LC11 displayed enhanced survival in macrophages in comparison with strain LC20 (4.0 +/- 0.2 versus 2.1 +/- 0.6 log CFU ml-1, P < 0.01) at 24 h [2].
• In this report, we show that when human osteosarcoma derived clonal cells (TE 85 clone F-5) (HOS), which are immortalized and nontumorigenic, undergo transformation following infection by Kirsten murine sarcoma virus (K-HOS) or by a chemical carcinogen [N-methyl-N-nitro-N-nitrosoguanidine (MNNG-HOS)], the smooth muscle MLC-2 mRNA is repressed [3].
• Four bioassays were run for each phenol and yielded the following mean PE LC20 values (mg 1(-1)) in descending order of toxicity: p-aminophenol, 0.06; hydroquinone, 0.13; phenol, 0.70; p-nitrophenol, 0.81; p-cyanophenol, 3.0; p-chlorophenol, 3.3; p-hydroxyacetophenone, 4.2; p-hydroxybenzyl alcohol, 6.4; and p-hydroxybenzoic acid, 170 [4].

High impact information on MYL9

• By contrast, in rounded ROCK-dependent movement, where MLC2 phosphorylation is higher, MRCK has a smaller role [5].
• Signalling downstream of the small GTPase Rho increases contractility through Rho-kinase (ROCK)-mediated regulation of myosin-II light chain (MLC2) phosphorylation [5].
• Pivotal in this process is phosphorylation of myosin light chain-2 (MLC2) by Rho kinase (ROCK) downstream of Rho activation, which generates the contractile force necessary to drive disassembly of epithelial cell-cell junctions and cell-matrix adhesions at the rear of migrating cells [6].
• Endosomes generate localized Rho-ROCK-MLC2-based contractile signals via Endo180 to promote adhesion disassembly [6].
• We found no evidence of serine 1,2 phosphorylation at any time during mitosis on LC20 from cortically associated myosin [7].

Biological context of MYL9

• Phosphorylation of MLC-2 by the enzyme MLC kinase increases the actin-activated myosin ATPase activity and thereby regulates the contractile activity [8].
• The derived amino acid sequence of the putative human smooth muscle MLC-2 shows only three amino acid differences when compared to chicken gizzard MLC-2 [8].
• We have isolated and characterized an MLC-2 cDNA corresponding to the human vascular smooth muscle MLC-2 isoform from a cDNA library derived from umbilical artery RNA [8].
• Diphosphorylated MRLC is required for organization of stress fibers in interphase cells and the contractile ring in dividing cells [9].
• The MLC-2 open reading frame of 516 nucleotides encoding a protein of 172 residues was detected in cloned cDNA of 967 nucleotides [10].

Anatomical context of MYL9

• The 20-kDa regulatory myosin light chain (MLC), also known as MLC-2, plays an important role in the regulation of both smooth muscle and nonmuscle cell contractile activity [8].
• The translation of the in vitro synthesized mRNA, corresponding to the cDNA insert, in a rabbit reticulocyte lysate results in the synthesis of a 20,000-dalton protein that is immunoreactive with antibodies raised against purified chicken gizzard MLC-2 [8].
• In contrast, the human smooth muscle MLC-2 cDNA that we have characterized from an intact smooth muscle tissue is not expressed in skeletal and cardiac muscles and also in a number of nonmuscle cells.(ABSTRACT TRUNCATED AT 250 WORDS)[8]
• Blot hybridizations and S1 nuclease analysis indicate that the human smooth muscle MLC-2 isoform is expressed restrictively in smooth muscle tissues such as colon and uterus and in some, but not all, nonmuscle cell lines [8].
• Taken together, our data suggest that diphosphorylation of MRLC plays an important role in regulating actin filament assembly and reorganization in nonmuscle cells [9].

Associations of MYL9 with chemical compounds

• Phosphoserine was recovered by the phosphoamino acid analysis of MRLC phosphorylated by RSK-2 [11].
• Two moles of phosphate are incorporated into tyrosine per mol of LC20 [12].
• To further assess the role of this subunit in the intramolecular folding of myosin, LC20 was removed from turkey gizzard myosin at elevated temperatures in the presence of EDTA through the use of an antibody affinity column [13].
• Conversely, the treatment of cells with a specific inhibitor of Rho-kinase, Y-27632, resulted in the decrease of endogenous diphosphorylated MRLC and actin stress fibers [14].
• These effects of hZIPK were suppressed by the coexpression of a mutant MRLC where both phosphorylation sites were replaced with alanine, indicating that the changes in actin organization were a consequence of MRLC diphosphorylation [15].

Regulatory relationships of MYL9

• More than half of type I fibres in both soleus (65%) and quadriceps (68%) muscles also expressed 'fast' MLC3 and 36% of the type II fibres from quadriceps muscle expressed the slow isoform of MLC2 [16].

Other interactions of MYL9

• Two full-length cDNA clones encoding the skeletal myosin light chain 2 (MLC2; 1452bp) and myosin light chain 3 (MLC3; 972bp) were isolated from a cDNA library prepared from gilthead sea bream Sparus aurata larvae [17].
• Cleavage of either Mercenaria RLC (MRLC) or Macrocallista RLC (VLC) at its 3 Arg yielded four peptides, three of which could not be sequenced directly, due to an N-terminal blocking group and 2 Arg-Gln bonds in these proteins [18].
• CONCLUSIONS: The findings indicated that hU-II increased force of contraction in human heart via a PKC-dependent mechanism and increased phosphorylation of MLC-2, although this was independent of PKC [19].

Analytical, diagnostic and therapeutic context of MYL9

• As assessed by in situ hybridization, immunofluorescence, and luminescence assays of luciferase reporter activity in various regions of the heart, both the endogenous MLC-2 gene and the MLC-2 luciferase fusion gene were expressed exclusively in the ventricular compartment, with expression in the atrium at background levels [20].
• Here we found that Rho-kinase has an activity for MRLC diphosphorylation in nonmuscle cells using sequential column chromatographies [14].
• Peptide mapping revealed that transient transfection of hZIPK into HeLa cells caused diphosphorylation of MRLC [15].
• METHODS: Quantitative distributions of myosin heavy chain (MHC) and regulatory myosin light chain (MLC2) isoforms in atrial myocardium from 35 adult baboons were determined by electrophoresis under denaturing conditions and laser densitometry [21].
• In DCM patients, the spot intensity (protein abundance) of MLC2 is increased to 336% and HSP 27 is decreased to 59%, compared to the control group [22].

References