Ral Signals through a MAP4 Kinase-p38 MAP Kinase Cascade in C. elegans Cell Fate Patterning.

Autor:	Shin H; Center for Translational Cancer Research, Institute of Biosciences and Technology, Texas A&M Health Science Center, Houston, TX 77030, USA., Kaplan REW; Department of Pharmacology and Lineberger Comprehensive Cancer Center, University of North Carolina, Chapel Hill, Chapel Hill, NC 27599, USA., Duong T; Center for Translational Cancer Research, Institute of Biosciences and Technology, Texas A&M Health Science Center, Houston, TX 77030, USA., Fakieh R; Center for Translational Cancer Research, Institute of Biosciences and Technology, Texas A&M Health Science Center, Houston, TX 77030, USA., Reiner DJ; Center for Translational Cancer Research, Institute of Biosciences and Technology, Texas A&M Health Science Center, Houston, TX 77030, USA; Department of Medical Physiology, College of Medicine, Texas A&M University, College Station, TX 77843, USA; Department of Pharmacology and Lineberger Comprehensive Cancer Center, University of North Carolina, Chapel Hill, Chapel Hill, NC 27599, USA. Electronic address: dreiner@ibt.tamhsc.edu.
Jazyk:	angličtina
Zdroj:	Cell reports [Cell Rep] 2018 Sep 04; Vol. 24 (10), pp. 2669-2681.e5.
DOI:	10.1016/j.celrep.2018.08.011
Abstrakt:	C. elegans vulval precursor cell (VPC) fates are patterned by an epidermal growth factor (EGF) gradient. High-dose EGF induces 1° VPC fate, and lower dose EGF contributes to 2° fate in support of LIN-12/Notch. We previously showed that the EGF 2°-promoting signal is mediated by LET-60/Ras switching effectors, from the canonical Raf-MEK-ERK mitogen-activated protein (MAP) kinase cascade that promotes 1° fate to the non-canonical RalGEF-Ral that promotes 2° fate. Of oncogenic Ras effectors, RalGEF-Ral is by far the least well understood. We use genetic analysis to identify an effector cascade downstream of C. elegans RAL-1/Ral, starting with an established Ral binding partner, Exo84 of the exocyst complex. Additionally, RAL-1 signals through GCK-2, a citron-N-terminal-homology-domain-containing MAP4 kinase, and PMK-1/p38 MAP kinase cascade to promote 2° fate. Our study delineates a Ral-dependent developmental signaling cascade in vivo, thus providing the mechanism by which lower EGF dose is transduced. (Copyright © 2018 The Authors. Published by Elsevier Inc. All rights reserved.)
Databáze:	MEDLINE
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