V

CELL MEMBRANE

CELL MEMBRANE

Figure 4.2. Regulation of JAK/STAT signaling. Ligand (cytokine) binding leads to receptor phosporylation and subsequent activation of STAT molecules which dimerize; the complex thereafter translocates to the nucleus and activates transcription. SOCS is one class of molecules induced in response to specific cytokines and it down-regulates signaling mainly via inhibition of JAKs. SHP and PIAS are constitutive inhibitors that act on JAK and STAT molecules, respectively.

In the context of the present survey, it is interesting to note that SOCS1 and SOCS3 are expressed in the SCN, where the level of their transcripts displays a circadian fluctuation (Sadki et al. 2006).

This could represent a potent regulatory mechanism accounting for day/night differences in sensitivity of the biological clock to inflammatory molecules. We are presently studying whether SOCS can be expressed in neurons and whether this occurs also in brain areas involved in sleep regulation after an inflammatory challenge.

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