For Research Use Only. Not for use in diagnostic procedures.

Chromosome: 3; NC_000003.11 (123331143..123603149, complement). Location: 3q21

Synthetic peptide

Highly Purified
~95%. Purified by HPLC

Supplied as a lyophilized powder

Lyophilized powder may be stored at 4 degree C for short-term only. Stable for 12 months at -20 degree C. Reconstitute to nominal volume (see reconstitution instructions for peptides) and store at -20 degree C. For maximum recovery of product, centrifuge the original vial prior to removing the cap. Further dilutions can be made in assay buffer.

Small volumes of MYLK peptide vial(s) may occasionally become entrapped in the seal of the product vial during shipment and storage. If necessary, briefly centrifuge the vial on a tabletop centrifuge to dislodge any liquid in the container`s cap. Certain products may require to ship with dry ice and additional dry ice fee may apply.

Molecular Biology; MB-Myosin

210,715 Da[Similar Products]

myosin light chain kinase

myosin light chain kinase, smooth muscle; telokin; kinase-related protein; myosin, light polypeptide kinase; smooth muscle myosin light chain kinase

Myosin light chain kinase, smooth muscle

MLCK; MLCK1; MYLK1; MLCK; smMLCK; KRP??[Similar Products]

MYLK_HUMAN

This gene, a muscle member of the immunoglobulin gene superfamily, encodes myosin light chain kinase which is a calcium/calmodulin dependent enzyme. This kinase phosphorylates myosin regulatory light chains to facilitate myosin interaction with actin filaments to produce contractile activity. This gene encodes both smooth muscle and nonmuscle isoforms. In addition, using a separate promoter in an intron in the 3' region, it encodes telokin, a small protein identical in sequence to the C-terminus of myosin light chain kinase, that is independently expressed in smooth muscle and functions to stabilize unphosphorylated myosin filaments. A pseudogene is located on the p arm of chromosome 3. Four transcript variants that produce four isoforms of the calcium/calmodulin dependent enzyme have been identified as well as two transcripts that produce two isoforms of telokin. Additional variants have been identified but lack full length transcripts. [provided by RefSeq, Jul 2008]

Function: 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 Ca2+ 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. Ref.4 Ref.7 Ref.15 Ref.17 Ref.19 Ref.20 Ref.21 Ref.23 Ref.27 Ref.28 Ref.29 Ref.32 Ref.33

Catalytic activity: ATP + [myosin light-chain] = ADP + [myosin light-chain] phosphate.

Cofactor: Magnesium.Calcium.

Enzyme regulation: Isoform 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. Ref.4 Ref.15 Ref.16 Ref.19 Ref.20 Ref.34

Subunit structure: All isoforms including Telokin bind calmodulin. Interacts with SVIL

By similarity. Interacts with CTTN; this interaction is reduced during thrombin-induced endothelial cell (EC) contraction but is promoted by the barrier-protective agonist sphingosine 1-phosphate (S1P) within lamellipodia. A complex made of ABL1, CTTN and MYLK regulates cortical actin-based cytoskeletal rearrangement critical to sphingosine 1-phosphate (S1P)-mediated endothelial cell (EC) barrier enhancement. Binds to NAA10/ARD1 and PTK2B/PYK2. Ref.14 Ref.23 Ref.27 Ref.30 Ref.31

Subcellular location: Cytoplasm. Cell projection ? lamellipodium. Cleavage furrow. Cytoplasm ? cytoskeleton. Note: Localized to stress fibers during interphase and to the cleavage furrow during mitosis. Ref.7 Ref.30

Tissue specificity: Smooth muscle and non-muscle isozymes are expressed in a wide variety of ***** and fetal tissues and in cultured endothelium with qualitative expression appearing to be neither tissue- nor development-specific. Non-muscle isoform 2 is the dominant splice variant expressed in various tissues. Telokin has been found in a wide variety of ***** and fetal tissues. Accumulates in well differentiated enterocytes of the intestinal epithelium in response to tumor necrosis factor (TNF). Ref.1 Ref.5 Ref.18 Ref.30

Induction: Accumulates in individuals with asthma (at protein levels). Induced by tumor necrosis factor (TNF). Repressed by androgens (e.g. R1881). Ref.4 Ref.15 Ref.16 Ref.18 Ref.19 Ref.20 Ref.26 Ref.34 Ref.35

Post-translational modification: Can probably be down-regulated by phosphorylation. Tyrosine phosphorylation by ABL1 increases kinase activity, reverses MLCK-mediated inhibition of Arp2/3-mediated actin polymerization, and enhances CTTN-binding. Phosphorylation by SRC at Tyr-464 and Tyr-471 promotes CTTN binding.The C-terminus is deglutamylated by AGTPBP1/ CCP1, AGBL1/CCP4 and AGBL4/CCP6, leading to the formation of Myosin light chain kinase, smooth muscle, deglutamylated form. The consequences of C-terminal deglutamylation are unknown

By similarity.Acetylated at Lys-608 by NAA10/ARD1 via a calcium-dependent signaling; this acetylation represses kinase activity and reduces tumor cell migration.

Involvement in disease: Familial aortic aneurysm thoracic 7 (AAT7) [MIM:613780]: A disease characterized by permanent dilation of the thoracic aorta usually due to degenerative changes in the aortic wall. It is primarily associated with a characteristic histologic appearance known as 'medial necrosis' or 'Erdheim cystic medial necrosis' in which there is degeneration and fragmentation of elastic fibers, loss of smooth muscle cells, and an accumulation of basophilic ground substance.Note: The disease is caused by mutations affecting the gene represented in this entry. Ref.39

Miscellaneous: 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.

Sequence similarities: Belongs to the protein kinase superfamily. CAMK Ser/Thr protein kinase family.Contains 1 fibronectin type-III domain.Contains 9 Ig-like C2-type (immunoglobulin-like) domains.Contains 1 protein kinase domain.

Biophysicochemical propertiesKinetic parameters:KM=6.5 μM for MLC (isoform 1 at 22 degrees Celsius) Ref.4KM=7.2 μM for MLC (isoform 2 at 22 degrees Celsius)Vmax=11.9 μmol/min/mg enzyme (isoform 1 at 22 degrees Celsius)Vmax=10.9 μmol/min/mg enzyme (isoform 1 at 22 degrees Celsius)

Sequence caution: The sequence AAD15922.1 differs from that shown. Reason: Frameshift at position 1433. The sequence AAD15923.1 differs from that shown. Reason: Frameshift at position 1433. The sequence AAD15924.1 differs from that shown. Reason: Frameshift at position 1433. Isoform 3A: The sequence AAD15922.1 differs from that shown. Reason: Frameshift at positions 1433 and 1439. Isoform 3B: The sequence AAD15923.1 differs from that shown. Reason: Frameshift at positions 1433 and 1439. Isoform 4: The sequence AAD15924.1 differs from that shown. Reason: Frameshift at positions 1433 and 1439.

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