The Caenorhabditis elegans protein SOC-3 permits an alternative mode of signal transduction by the EGL-15 FGF receptor.

Autor: Rodriguez Torres CS; Department of Biological Sciences, University of Wisconsin-Milwaukee, Milwaukee, WI, 53201, USA., Wicker NB; Department of Biological Sciences, University of Wisconsin-Milwaukee, Milwaukee, WI, 53201, USA., Puccini de Castro V; Department of Biology, Northeastern Illinois University, Chicago, IL, 60625, USA., Stefinko M; Department of Biology, Northeastern Illinois University, Chicago, IL, 60625, USA., Bennett DC; Yale University School of Medicine, New Haven, CT, 06520, USA., Bernhardt B; Department of Biology, Ithaca College, Ithaca, NY, 14850, USA., Garcia Montes de Oca M; Department of Biology, Northeastern Illinois University, Chicago, IL, 60625, USA., Jallow S; Department of Biology, Ithaca College, Ithaca, NY, 14850, USA., Flitcroft K; Department of Biological Sciences, University of Wisconsin-Milwaukee, Milwaukee, WI, 53201, USA., Palalay JS; Department of Biology, Northeastern Illinois University, Chicago, IL, 60625, USA., Payán Parra OA; Department of Biology, Northeastern Illinois University, Chicago, IL, 60625, USA., Stern YE; Department of Thoracic Oncology, H. Lee Moffitt Cancer Center & Research Institute, Tampa, FL, 33612, USA., Koelle MR; Yale University School of Medicine, New Haven, CT, 06520, USA., Voisine C; Department of Biology, Northeastern Illinois University, Chicago, IL, 60625, USA., Woods IG; Department of Biology, Ithaca College, Ithaca, NY, 14850, USA., Lo TW; Department of Biology, Ithaca College, Ithaca, NY, 14850, USA., Stern MJ; Department of Biology, Northeastern Illinois University, Chicago, IL, 60625, USA., de la Cova CC; Department of Biological Sciences, University of Wisconsin-Milwaukee, Milwaukee, WI, 53201, USA. Electronic address: delacova@uwm.edu.
Jazyk: angličtina
Zdroj: Developmental biology [Dev Biol] 2024 Dec; Vol. 516, pp. 183-195. Date of Electronic Publication: 2024 Aug 21.
DOI: 10.1016/j.ydbio.2024.08.014
Abstrakt: Fibroblast Growth Factors and their receptors (FGFRs) comprise a cell signaling module that can stimulate signaling by Ras and the kinases Raf, MEK, and ERK to regulate animal development and homeostatic functions. In Caenorhabditis elegans, the sole FGFR ortholog EGL-15 acts with the GRB2 ortholog SEM-5 to promote chemoattraction and migration by the sex myoblasts (SMs) and fluid homeostasis by the hypodermis (Hyp7). Cell-specific differences in EGL-15 signaling were suggested by the phenotypes caused by egl-15(n1457), an allele that removes a region of its C-terminal domain (CTD) known to bind SEM-5. To determine how mutations altered EGL-15 activity in the SMs and Hyp7, we used the kinase reporter ERK-KTR to measure activation of the ERK ortholog MPK-1. Consequences of egl-15(n1457) were cell-specific, resulting in loss of MPK-1 activity in the SMs and elevated activity in Hyp7. Previous studies of Hyp7 showed that loss of the CLR-1 phosphatase causes a fluid homeostasis defect termed "Clear" that is suppressed by reduction of EGL-15 signaling, a phenotype termed "Suppressor of Clear" (Soc). To identify mechanisms that permit EGL-15 signaling in Hyp7, we conducted a genetic screen for Soc mutants in the clr-1; egl-15(n1457) genotype. We report the identification of SOC-3, a protein with putative SEM-5-binding motifs and PH and PTB domains similar to DOK and IRS proteins. In combination with the egl-15(n1457) mutation, loss of either soc-3, the GAB1 ortholog soc-1, or the SHP2 ortholog ptp-2, reduced MPK-1 activation. We generated alleles of soc-3 to test the requirement for the SEM-5-binding motifs, finding that residue Tyr 356 is required for function. We propose that EGL-15-mediated SM chemoattraction relies solely on the direct interaction between SEM-5 and the EGL-15 CTD. In Hyp7, EGL-15 signaling uses two mechanisms: the direct SEM-5 binding mechanism; and an alternative, CTD-independent mechanism involving SOC-3, SOC-1, and PTP-2. This work demonstrates that FGF signaling uses distinct, tissue-specific mechanisms in development, and identifies SOC-3 as a potential adaptor that facilitates Ras pathway activation by FGFR.
(Copyright © 2024 Elsevier Inc. All rights reserved.)
Databáze: MEDLINE
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