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Simultaneous monitoring of STAT1 STAT3 and STAT5 activations in response to type I interferons by multiplex bead immunoassay
Author(s) -
Surby Mark,
Zheng Wei,
Sarreal Deanna,
Wang Jimin,
Reagan Kevin
Publication year - 2008
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.22.2_supplement.571
Subject(s) - stat5 , stat1 , multiplex , stat , janus kinase , stat protein , stat3 , signal transduction , jak stat signaling pathway , stat4 , biology , phosphorylation , microbiology and biotechnology , interferon , immunology , bioinformatics , tyrosine kinase
The type I interferons (IFNs) are pleiotropic cytokines that regulate many different cellular functions. The major signaling pathway activated by type I IFNs involves sequential phosphorylation and activation of the Janus kinase (JAK) and signal transducers and activators of transcription (STAT) proteins, providing the primary mechanism through which gene expression is induced. The type I IFNs are unique among all cytokines that they can activate all seven known STATs. Once activated, many different STAT homodimer or heterodimer combinations can form in response to type I IFN. A method to measure various active STAT proteins simultaneously will significantly expedite the drug discovery process targeting this pathway. In this study, cell lines from T cell leukemia, promonocytic cells, erythroleukemia and NK cells were treated with either INF‐α or INF‐β. The activation of the STAT1, STAT3 and STAT5 (STAT5a and STAT5b) were monitored concurrently using the multiplex bead immunoassay. The results demonstrate that blood cells respond differentially to type I INFs, creating unique STAT activation patterns. It is plausible that the differential and unique STAT activation patterns target functionally distinct genes, through which IFNs elicit different biological functions. Our study illustrates that simultaneous monitoring of the STATs activations allows a more complete cell‐based analysis of INF signal transduction mechanisms and provides a valuable tool for research and drug discovery.