smMLCK: 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. Defects in MYLK are the cause of familial aortic aneurysm thoracic type 7 (AAT7). AAT7 is 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. Belongs to the protein kinase superfamily. CAMK Ser/Thr protein kinase family. 8 isoforms of the human protein are produced by alternative splicing.
Protein type: CAMK group; EC 2.7.11.18; Kinase, protein; MLCK family; Protein kinase, CAMK; Protein kinase, Ser/Thr (non-receptor)
Chromosomal Location of Human Ortholog: 16|16 B3
Cellular Component: cell projection; cleavage furrow; cytoplasm; cytoskeleton; extracellular exosome; intercellular junction; lamellipodium; stress fiber
Molecular Function: actin binding; ATP binding; calmodulin binding; enzyme binding; kinase activity; metal ion binding; myosin light chain kinase activity; nucleotide binding; protein binding; protein kinase activity; protein serine/threonine kinase activity; transferase activity
Biological Process: bleb formation; cellular hypotonic response; cellular response to calcium ion; phosphorylation; positive regulation of calcium ion transport; positive regulation of cell migration; positive regulation of wound healing; protein amino acid phosphorylation; smooth muscle contraction; tonic smooth muscle contraction
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