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Biochemistry: Wouter Moolenaar

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Wouter Moolenaar, Ph.D. professorGroup leader, professor

About Wouter Moolenaar

Lipid Growth Factor Signaling

The Autotaxin-LPA Signaling Axis
LPA is an extracellular signaling molecule that acts through multiple G protein-coupled receptors present in numerous cell types.LPA receptor signaling is implicated in a wide variety of physiological and pathological processes, ranging from vascular development to metastasis. The classical LPA receptors stimulate cell migration and proliferation, and are implicated in cell transformation and metastasis. Newly identified LPA receptors can mediate inhibitory responses, which renders the global LPA signaling picture increasingly complex. One challenge is to understand how distinct LPA receptors cooperate, to predict the biological outcome of LPA stimulation in a given cell type.
 
Autotaxin
Autotaxin (ATX) is the major LPA-producing enzyme in plasma and tissues. We are analyzing the function of autotaxin using multiple approaches, including structural studies and the development of mouse models and small-molecule inhibitors. The knockout mouse revealed an unexpected function for ATX in vascular development. Furthermore, the structure of ATX revealed novel features, notably the presence of a deep lipid-binding pocket and a nearby open tunnel, which we are now further investigating (collaboration A. Perrakis). Our studies have provided new insights into the mode of action of ATX, and how it delivers LPA to target cells. Targeting the ATX-LPA signaling axis may prove a valuable strategy for inhibiting tumor cell growth and metastasis.

Key publications View All Publications

  • Structural basis of substrate discrimination and integrin binding by autotaxin

    (2011) Nat Struct Mol Biol.; 18: 198-204

    Hausmann J, Kamtekar S, Christodoulou E, Day JE, Wu T, Fulkerson Z, Albers HM, van Meeteren LA, Houben AJ, van Zeijl L, Jansen S, Andries M, Hall T, Pegg LE, Benson TE, Kasiem M, Harlos K, Kooi CW, Smyth SS, Ovaa H, Bollen M, Morris AJ, Moolenaar WH, Perrakis A.
     

    Link to PubMed
  • Autotaxin: structure-function and signaling

    (2014) J Lipid Res. Feb 18;55(6):1010-1018. [Epub ahead of print]

    Perrakis A, Moolenaar WH.

    Link to PubMed
 
 

Recent publications View All Publications

  • Autotaxin determines colitis severity in mice and is secreted by B cells in the colon

    (2019) FASEB J. Mar;33(3):3623-3635.

    Lin S, Haque A, Raeman R, Guo L, He P, Denning TL, El-Rayes B, Moolenaar WH, Yun CC.

    Link to PubMed
  • Profilin binding couples chloride intracellular channel protein CLIC4 to RhoA-mDia2 signaling and filopodium formation

    (2018) J Biol Chem. Dec 14;293(50):19161-19176.

    Argenzio E, Klarenbeek J, Kedziora KM, Nahidiazar L, Isogai T, Perrakis A, Jalink K, Moolenaar WH, Innocenti M.

    Link to PubMed
 

Contact

  • Office manager

    Mirna Ekelschot - van Diermen

  • E-mail

    m.v.diermen@nki.nl

  • Telephone Number

    +31 20 512 9127

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