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Quantitative Analysis of Cross‐Talk Between RET and Other Growth Factor Receptors
Author(s) -
Huestis Mikayla Joy,
Chow Jennifer
Publication year - 2016
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.30.1_supplement.1131.2
Subject(s) - crosstalk , receptor tyrosine kinase , mapk/erk pathway , signal transduction , microbiology and biotechnology , protein kinase b , receptor , transcription factor , biology , growth factor receptor , pi3k/akt/mtor pathway , gene , genetics , physics , optics
RET ( Re arranged During T ransfection) is a receptor tyrosine kinase, involved in neuronal and kidney development, that activates multiple signaling cascades, including the Raf/MEK/ERK MAP Kinase and Akt pathways. We developed a luciferase reporter gene assay that is responsive to MAP Kinase pathway activation, and used it to investigate RET signaling dynamics from receptor activation to gene transcription and translation, and to quantitatively characterize crosstalk between RET and other receptor signaling pathways. The results showed that the first committed step in RET‐activated protein expression is gene transcription. Previous studies from the Hynes and Tufro laboratories have shown that crosstalk between RET and other receptors has biological importance. However, quantitative analysis of crosstalk between growth factor receptors has rarely been investigated. We used our luciferase assay, in conjunction with ELISAs measuring the amplitude and dynamics of ERK and Akt signaling, and assays measuring functional cellular outcomes, to screen for growth factors and corresponding receptors involved in cross‐talk with RET, and to achieve quantitative insights into the interaction between the pathways and its functional significance. Support or Funding Information Arnold and Mabel Beckman Foundation, National Institutes of Health, Biogen Idec