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The Coordination of Notch and Integrin Signaling by Resveratrol
Author(s) -
LaFoya Bryce,
Albig Allan
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.868.2
Subject(s) - notch signaling pathway , microbiology and biotechnology , integrin , signal transduction , hes3 signaling axis , crosstalk , cyclin dependent kinase 8 , biology , cell signaling , resveratrol , cell fate determination , angiogenesis , collagen receptor , transcription factor , chemistry , cell , cancer research , biochemistry , physics , gene , optics
Integrins are transmembrane proteins which form for cell‐cell and cell‐extracellular matrix connections, allowing environmental signals to be relayed into a cell through their signal transduction capabilities. The Notch signaling pathway has a role in many cellular processes such as differentiation and proliferation. The regulation of this pathway can provide a cell with molecular cues which are used to make cell‐fate decisions. Both αVβ3 integrin and Notch signaling have been implicated in many normal processes of vascular biology such as angiogenesis and arteriovenous development as well as pathological processes such as the development of atherosclerosis and tumor vascularization. Studies on trans‐resveratrol, a stilbene produced in several plant species, have demonstrated beneficial effects on vascular health. Resveratrol is known to regulate two important signaling pathways in endothelial biology: Notch and αVβ3 integrin signaling. Through luciferase reporter assays and western blot analysis we have demonstrated that trans‐resveratrol promotes Notch1 induced transcriptional activation, but does not show the same effect when siRNA is used to knockdown β3 integrin. This data suggests, that resveratrol is able to induce transcription of Notch target genes via an αVβ3 dependent mechanism. Using co‐immunoprecipitation and in vitro kinase assays, we have identified an interaction between Notch1 and SRC kinase, a principle intermediary of integrin signaling. Additionally, using site directed mutagenesis we have identified tyrosine residues within the transcriptionally active portion of Notch1 which are important for Notch activation. Having established these results, we turn our attention towards the importance of the Notch1‐αVβ3 integrin signaling axis in the major cellular hallmarks of atherosclerosis. Support or Funding Information Boise State Biomolecular Sciences Ph.D. Program NIH #1R15GM102852‐01