Robustness and Information Transfer within IL-6-induced JAK/STAT Signalling

Area of Science:

• Cellular Biology
• Systems Biology
• Biophysics

Background:

• Cellular communication is vital, yet protein expression and activation vary even in identical cells.
• Understanding how cells maintain function amidst this heterogeneity is crucial for biological processes.

Purpose of the Study:

• To investigate mechanisms ensuring reliable Interleukin-6 (IL-6) induced Janus Kinase/Signal Transducer and Activator of Transcription (JAK/STAT) signalling despite cell-to-cell variability.
• To apply information theory to quantify signalling robustness and channel capacity.

Main Methods:

• Utilized information theory to analyze JAK/STAT signalling dynamics.
• Investigated the roles of STAT3 expression, STAT3 phosphorylation (tyrosine and serine), and SOCS3 in signalling robustness and channel capacity.

Main Results:

• Signalling robustness varies with cytokine concentration, STAT3 expression levels, and STAT3 phosphorylation.
• Early STAT3 activation is robust at low cytokine levels; high levels require high STAT3 expression or serine phosphorylation.
• The feedback inhibitor SOCS3 enhances robustness later in signalling.
• Cell-to-cell variability in STAT3 expression limits JAK/STAT signalling channel capacity.
• Increasing STAT3 expression enhances both channel capacity and robustness.
• Increasing STAT3 tyrosine phosphorylation enhances channel capacity but reduces robustness.

Conclusions:

• Multiple mechanisms cooperate to ensure robust JAK/STAT signalling and prevent dysregulation in the face of cellular heterogeneity.
• Information theory provides a framework for understanding how cells achieve reliable communication despite intrinsic variability.