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Time-resolved Förster Resonance Energy Transfer Assays for Measurement of Endogenous Phosphorylated STAT Proteins in Human Cells
Published on: September 9, 2021
Modulation of human JAK-STAT pathway signaling by functionally conserved regulators.
Patrick Müller1, Dhamayanthi Pugazhendhi, Martin P Zeidler
1Department of Molecular and Cellular Biology; Harvard University; Cambridge, MA USA.
JAK-STAT
|September 24, 2013
Summary
This study validates Drosophila melanogaster gene homologs as crucial regulators of the Janus kinase-Signal transducer and activator of transcription (JAK-STAT) pathway in humans. Most tested human genes showed regulatory roles, highlighting model systems for disease gene discovery.
Area of Science:
- Cellular signaling pathways
- Genetics and genomics
- Cancer biology
Background:
- The Janus kinase-Signal transducer and activator of transcription (JAK-STAT) pathway is conserved across species and implicated in human cancers.
- Genome-wide RNA interference (RNAi) screens in Drosophila identified key JAK-STAT pathway regulators.
Purpose of the Study:
- To analyze human homologs of Drosophila-identified JAK-STAT pathway regulators.
- To identify novel human genes involved in JAK-STAT signaling.
Main Methods:
- Analysis of 73 human genes representing Drosophila JAK-STAT pathway regulators.
- Utilized siRNA assays to assess STAT1 and STAT3 protein levels and phosphorylation.
- Measured expression of endogenous STAT1 and STAT3 transcriptional targets.
Main Results:
- Identified potential JAK-STAT pathway regulatory roles in 69 out of 73 (95%) tested human genes.
- Discovered a wide range of human JAK-STAT pathway regulators, including previously unknown modulators.
- Confirmed the utility of model organism-based screening for pathway regulator identification.
Conclusions:
- Human homologs of Drosophila JAK-STAT regulators are frequently involved in the pathway.
- This research expands the known repertoire of human JAK-STAT pathway regulators.
- Identified genes may be implicated in human diseases associated with JAK-STAT pathway misregulation.
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