Jaks, Stats and the immune system

Changes in gene expression are necessary for an adaptive response of cells to immunological stimuli and thus for their proper function in the concert of the immune system. Regulatory inputs usually originate from cell surface receptors and in many cases affect the transcription rates of specific genes by modulating the activity of transcription factors. The Jak-Stat signalling paradigm has received large attention by molecular immunologists because it applies to nuclear signalling by all cytokine receptors. In its simplest form it requires only two protein components downstream of the receptor: Janus family protein tyrosine kinases (Jaks) which are usually receptor-associated, and signal transducer and activator of transcription (Stat) family transcription factors which carry the receptor-generated signal to the nucleus and stimulate gene expression. Here we give a brief overview of both recent progress and open questions concerning the Jak and Stat molecules, their regulation, and the biological implications of their activity.