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Resources » Paper

Shin H et al. (2018) Cell Rep "Ral Signals through a MAP4 Kinase-p38 MAP Kinase Cascade in C.elegans Cell Fate Patterning."

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  • Comments on Shin H et al. (2018) Cell Rep "Ral Signals through a MAP4 Kinase-p38 MAP Kinase Cascade in C.elegans Cell Fate Patterning." (0)

  • Overview

    PMID:
    30184501
    DOI:
    10.1016/j.celrep.2018.08.011
    Status:
    Publication type:
    Journal_article
    WormBase ID:
    WBPaper00055163

    Shin H, Kaplan REW, Duong T, Fakieh R, & Reiner DJ (2018). Ral Signals through a MAP4 Kinase-p38 MAP Kinase Cascade in C.elegans Cell Fate Patterning. Cell Rep, 24, 2669-2681.e5. doi:10.1016/j.celrep.2018.08.011

    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 ofLIN-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 invivo, thus providing the mechanism by which lower EGF dose is transduced.


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