Autotaxin – Active Enzyme
- Secreted human β isoform (teratocarcinoma derived) autotaxin with C-terminal 6-His tag was expressed in Sf9 cells and purified using nickel-NTA chromatography.
- Autotaxin, also known as ATX, eENPP2, lysophospholipase D, phosphodiesterase 1a, and plasma cell glycoprotein-1, is a secreted glycoprotein that is widely expressed with high levels in serum.
Via its lysophospholipase D (lysoPLD) activity autotaxin hydrolyzes lysophosphatidylcholine (LPC) to generate the phospholipid growth factor lysophosphatidic acid (LPA). The enzyme’s same
activity hydrolyzes sphingosylphosphorylcholine(SPC) to form sphingosine-1-phosphate (S1P).
- Autotaxin was first isolated as the autocrine motility factor secreted from melanoma cells. At that time the enzyme’s lysoPLD activity had not been identified, so it was classified by homology to
the ectonucleotide pyrophosphatase/phosphodiesterase (NPP) family of enzymes whose
members hydrolyze phosphodiester bonds in various nucleotides and nucleotide derivatives. It was initially unclear how nucleotide hydrolysis could lead to the stimulation of cell motility. This mystery
was solved when autotaxin was discovered to be identical to serum lysoPLD. Since then, the cancer-related activities of autotaxin, at least in cultured cells, have been attributed to the enzyme’s
lysoPLD activity. In addition to cancer, autotaxin has been implicated in a number of diseases including obesity, arthritis, multiple sclerosis, Alzheimer’s disease, and neuropathic pain.
- While autotaxin is a 100 kDa protein, post-translational modifications, such as glycosylations, contribute to it's migration at 125 kDa in SDS-PAGE.
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