Related Experiment Video
Updated: May 16, 2026

Time-resolved Förster Resonance Energy Transfer Assays for Measurement of Endogenous Phosphorylated STAT Proteins in Human Cells
Published on: September 9, 2021
The Jak/STAT signaling pathway is downregulated at febrile temperatures
Tobias Nespital1, Ger J Strous
1Department of Cell Biology and Institute of Biomembranes, University Medical Center Utrecht, Utrecht, The Netherlands.
Background:
The Janus family of kinases (JAKs), Jak1, Jak2, Jak3, and Tyk2, constitute a subgroup of non-receptor protein tyrosine kinases. Upon cytokine binding, the receptor-associated kinases are activated and phosphorylate tyrosine residues in their cognate cytokine receptors. Their activities are controlled at several levels and include cellular concentration, auto-activation, and degradation.
Principal Findings:
Our findings show that elevated temperatures in the fever range irreversibly aggregate Jak2 and considerably reduce functional Jak2 protein levels. Jak2 synthesis remains unaltered. We observed that also the protein level of the signal transducer and activator of transcription, STAT5b, is transiently decreased at temperatures above 37°C. Consequently, the signaling response, e.g. via the growth hormone receptor, is reduced.
Conclusions/Significance:
These findings predict that elevated body temperatures lower the responsiveness of cytokine receptors.
Related Concept Videos
The JAK-STAT Signaling Pathway
Increased Body Temperature
Methods of reducing fever
Pharmacological Methods of Reducing Fever:
NF-κB-dependent Signaling Pathway
NF-κB-dependent Signaling Mechanism
The heterodimer of NF-κB...
Decreased Body Temperature
Acute Inflammation III: Local and Systemic Effects