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Insights into autotaxin: how to produce and present a lipid mediator

Abstract

Autotaxin (ATX) is a secreted phosphodiesterase that produces the lipid mediator lysophosphatidic acid (LPA). LPA acts through specific guanine-nucleotide-binding protein (G protein)-coupled receptors to stimulate migration, proliferation, survival and other functions in many cell types. ATX is important in vivo for processes as diverse as vasculogenesis, lymphocyte trafficking and tumour progression. However, the inner workings of ATX have long been elusive, in terms of both its substrate specificity and how localized LPA signalling is achieved. Structural studies have shown how ATX recognizes its substrates and may interact with the cell surface to promote specificity in LPA signalling.

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Figure 1: ATX–LPA receptor signalling.
Figure 2: The structure of ATX.
Figure 3: Association of ATX with cell-surface molecules may promote LPA targeting.

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Acknowledgements

We apologize to those authors whose work could not be referenced directly because of space limitations. W.H.M. and A.P. are supported by grants from the Dutch Cancer Society (KWF) and the Netherlands Organisation for Scientific Research (NWO).

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Moolenaar, W., Perrakis, A. Insights into autotaxin: how to produce and present a lipid mediator. Nat Rev Mol Cell Biol 12, 674–679 (2011). https://doi.org/10.1038/nrm3188

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