MYLK - Myosin light chain kinase, smooth muscle - human protein (Function)
 
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MYLK »  Myosin light chain kinase, smooth muscle   [ EC 2.7.11.18 ]  (MLCK)
 
Protein also known as:  Kinase-related protein (KRP). Cleaved into:  Myosin light chain kinase, smooth muscle, deglutamylated form.
Gene name:  MYLK
Entry whose protein(s) existence is based on evidence at protein level
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GENE REF ISO

Function

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Overview 
Calcium/calmodulin-dependent myosin light chain kinase implicated in smooth muscle contraction via phosphorylation of myosin light chains (MLC). Also regulates actin-myosin interaction through a non-kinase activity. Phosphorylates PTK2B/PYK2 and myosin light-chains. Involved in the inflammatory response (e.g. Apoptosis, vascular permeability, leukocyte diapedesis), cell motility and morphology, airway hyperreactivity and other activities relevant to asthma. Required for tonic airway smooth muscle contraction that is necessary for physiological and asthmatic airway resistance. Necessary for gastrointestinal motility. Implicated in the regulation of endothelial as well as vascular permeability, probably via the regulation of cytoskeletal rearrangements. In the nervous system it has been shown to control the growth initiation of astrocytic processes in culture and to participate in transmitter release at synapses formed between cultured sympathetic ganglion cells. Critical participant in signaling sequences that result in fibroblast apoptosis. Plays a role in the regulation of epithelial cell survival. Required for epithelial wound healing, especially during actomyosin ring contraction during purse-string wound closure. Mediates RhoA-dependent membrane blebbing. Triggers TRPC5 channel activity in a calcium-dependent signaling, by inducing its subcellular localization at the plasma membrane. Promotes cell migration (including tumor cells) and tumor metastasis. PTK2B/PYK2 activation by phosphorylation mediates ITGB2 activation and is thus essential to trigger neutrophil transmigration during acute lung injury (ALI). May regulate optic nerve head astrocyte migration. Probably involved in mitotic cytoskeletal regulation. Regulates tight junction probably by modulating ZO-1 exchange in the perijunctional actomyosin ring. Mediates burn-induced microvascular barrier injury; triggers endothelial contraction in the development of microvascular hyperpermeability by phosphorylating MLC. Essential for intestinal barrier dysfunction. Mediates Giardia spp.-mediated reduced epithelial barrier function during giardiasis intestinal infection via reorganization of cytoskeletal F-actin and tight junctional ZO-1. Necessary for hypotonicity-induced Ca(2+) entry and subsequent activation of volume-sensitive organic osmolyte/anion channels (VSOAC) in cervical cancer cells. Responsible for high proliferative ability of breast cancer cells through anti-apoptosis.  
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  • CuratedUniProtKB
GO molecular function 
Actin bindingdefinition[GO:0003779]  
  • IEAUniProtKB KW
ATP bindingdefinition[GO:0005524]  
  • IEAUniProtKB KW
Calmodulin bindingdefinition[GO:0005516]  
  • IEAUniProtKB KW
Calmodulin-dependent protein kinase activitydefinition[GO:0004683] silver  
  • IBARefGenome
Metal ion bindingdefinition[GO:0046872]  
  • IEAUniProtKB KW
Myosin light chain kinase activitydefinition[GO:0004687]  
1
  • IDAUniProtKB
Protein bindingdefinition[GO:0005515]  
1
  • IPIIntAct
GO biological process 
Actin filament organizationdefinition[GO:0007015] silver  
  • IBARefGenome
Aorta smooth muscle tissue morphogenesisdefinition[GO:0060414]  
1
  • IMPBHF-UCL
Bleb assemblydefinition[GO:0032060]  
1
  • IMPUniProtKB
Cellular hypotonic responsedefinition[GO:0071476]  
1
  • IDAUniProtKB
Positive regulation of calcium ion transportdefinition[GO:0051928]  
1
  • IDAUniProtKB
Positive regulation of cell migrationdefinition[GO:0030335]  
1
  • IDAUniProtKB
Positive regulation of wound healingdefinition[GO:0090303]  
1
  • IDAUniProtKB
Protein phosphorylationdefinition[GO:0006468] silver  
  • IEAInterPro 2 GO
Smooth muscle contractiondefinition[GO:0006939]  
  • ISSOrtholog Curator
  • IBARefGenome
Tonic smooth muscle contractiondefinition[GO:0014820]  
  • ISSOrtholog Curator
Enzymatic activity 
This protein acts as an enzyme. It is known to catalyze the following reaction
EC 2.7.11.18: ATP + [myosin light-chain] ADP + [myosin light-chain] phosphate.  
  • CuratedUniProtKB
It requires the following cofactors
Magnesium.  
  • CuratedUniProtKB
Calcium.  
  • CuratedUniProtKB
It is regulated in the following manner
Isoform  Iso 1   Is activated by phosphorylation on Tyr-464 and Tyr-471. Isoforms which lack these tyrosine residues are not regulated in this way. All catalytically active isoforms require binding to calcium and calmodulin for activation. Repressed by organometallic pyridylnaphthalimide complexes, wortmannin, ML-7 (a synthetic naphthalenesulphonyl derivative that inhibits the binding of ATP to MLCK) and ML-9.  
6
  • CuratedUniProtKB
 
More information is available from:
Pathways 
According to KEGG, this protein belongs to the following pathways:
Calcium signaling pathway  hsa04020+4638  
Focal adhesion  hsa04510+4638  
Gastric acid secretion  hsa04971+4638  
Regulation of actin cytoskeleton  hsa04810+4638  
Vascular smooth muscle contraction  hsa04270+4638  
According to Reactome, this protein belongs to the following pathway:
Smooth Muscle Contraction  REACT_20558  
Note 
In asthmatic patients, overexpression promotes actin filament propulsion, thus contributing to airway hyperresponsiveness. Some MYLK variants may contribute to acute lung injury (ALI) susceptibility. Potential therapeutic target in the treatment of burn edema.  
  • CuratedUniProtKB
 

Biophysicochemical properties

Kinetic parameters
KM 6.5 uM for MLC (isoform 1 at 22 degrees Celsius)
KM 7.2 uM for MLC (isoform 2 at 22 degrees Celsius)
Vmax 11.9 umol/min/mg enzyme (isoform 1 at 22 degrees Celsius)
Vmax 10.9 umol/min/mg enzyme (isoform 1 at 22 degrees Celsius)

Keywords

Molecular function 
Kinase  definition   [KW-0418]
Serine/threonine-protein kinase  definition   [KW-0723]
Transferase  definition   [KW-0808]
Technical term 
Reference proteome  definition   [KW-1185]
 

Further external links

Other
GeneWiki: MYLK
GenomeRNAi: 4638
PRO: PR:Q15746
Chemistry
GuidetoPHARMACOLOGY: 1552