Ral Signals through a MAP4 Kinase-p38 MAP Kinase Cascade in C.elegans Cell Fate Patterning.
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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.
author list (cited authors)
Shin, H., Kaplan, R., Duong, T., Fakieh, R., & Reiner, D. J.
complete list of authors
Shin, Hanna||Kaplan, Rebecca EW||Duong, Tam||Fakieh, Razan||Reiner, David J