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Identification of Novel Fibroblast Growth Factor Receptor Signaling Components
Author(s) -
Eichelberger Eric,
Webb Jason C.,
Stefinko Mariya,
Stern Michael J.,
Voisine Cindy,
Lo TeWen
Publication year - 2018
Publication title -
the faseb journal
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.709
H-Index - 277
eISSN - 1530-6860
pISSN - 0892-6638
DOI - 10.1096/fasebj.2018.32.1_supplement.662.11
Subject(s) - fibroblast growth factor receptor , biology , microbiology and biotechnology , signal transduction , fibroblast growth factor , receptor tyrosine kinase , phenotype , signal transducing adaptor protein , mutation , tyrosine kinase , genetics , receptor , gene
Fibroblast Growth Factor Receptors (FGFRs) are a type of receptor tyrosine kinase (RTK) that phosphorylate precise tyrosine residues. FGFRs play a role in diverse developmental pathways that mediate cell proliferation, cell migration, and cell survival. We use C. elegans as a model to better understand FGFR signaling specificity. In C. elegans , the EGL‐15 FGFR is imperative for sex myoblast migration and fluid homeostasis. Defects in the processes mediated by the C. elegans EGL‐15 FGFR result in striking phenotypes that can be used to discover components of the EGL‐15 signaling pathway. For example, hyperactivation of EGL‐15 results in the excessive accumulation of clear fluid within the worm's body (the Clr phenotype). The isolation of suppressor of Clr ( soc ) mutants has led to the identification of many of the core components of EGL‐15 signaling. A previous soc screen identified the SEM‐5 adaptor protein that links RTK activation to the activation of the RAS/MAPK pathway. An egl‐15 mutation, n1457 (a truncation mutation), that eliminates the known SEM‐5 binding sites (Y1009 and Y1087) on EGL‐15 does not confer a Soc phenotype indicating that a key component that links activated EGL‐15 to SEM‐5 has yet to be identified. To identify these missing components, we conducted a modified, “enhancer” soc screen in an egl‐15(n1457) background. Using CRISPR/Cas9, we are introducing mutations in the known SEM‐5 binding sites (Y1009 and Y1087) to determine if the Soc phenotype in newly identified genes is solely dependent on these binding sites. We are also using RNAi to verify the identity of a novel soc gene, cca‐1 . Additional genetic analyses and whole‐genome sequencing will be used to identify the molecular identities of additional suppressors identified in our enhancer screen. Support or Funding Information NIH R15 (GM122001) This abstract is from the Experimental Biology 2018 Meeting. There is no full text article associated with this abstract published in The FASEB Journal .