Chemical inhibition through conformational stabilization of Rho GTPase effectors.
作者： S. W. Deacon , J. R. Peterson
DOI: 10.1007/978-3-540-72843-6_18
关键词: Formins 、 PAK1 、 Cell polarity 、 Biology 、 Signal transduction 、 Cell biology 、 CDC42 、 GTPase 、 MDia1 、 Effector
摘要: The Rho family of small GTP-binding proteins can activate a large number downstream effectors and participate in wide variety biological processes, including cell motility, membrane trafficking, polarity, gene transcription, mitosis. Specific small-molecule inhibitors individual effector GTPases would be powerful tools to elucidate the contributions particular these processes. In this chapter we describe identification chemical inhibitor scaffolding protein neural-Wiskott-Aldrich syndrome (N-WASP), discovery its novel mechanism action, stabilization N-WASP’s native autoinhibited conformation. Inasmuch as several other GTPase are regulated by autoinhibition, discuss how regulatory could exploited molecules develop highly specific effectors. We illustrate concept with Rac/Cdc42 p21-activated kinase (Pak1) mammalian diaphanous-related formin (mDia1).
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