Signal Transduction by Cytokines

The interaction of cytokines with their specific cell surface receptors triggers the activation of intracellular signaling cascades that ultimately have effects on multiple cellular functions. The earliest event is the activation of Janus Kinase (Jak) family members, which then phosphorylate substrates crucial for the transduction of cytokine signals. One of the most important substrates is the family of signal transducer and activator of transcription (STAT) proteins.

All class I and class II cytokine receptors studied to date induce tryosine phosphorylation of the receptor through the activity of protein tyrosine kinases closely associated with the cytosolic domain of the receptors. Cytokine binding induces the association of the α and Β receptor subunits and activation of a family of protein tyrosine kinases called the Janus Kinase (JAK) family.

While cytokines generally utlize the Jak-Stat pathway for signal transduction, each cytokine receptor specifically recruits certain Jak and Stat proteins.

One of the most important pathways of cell survival mediated via signaling through the TNFR family is the activation of NF-κB.

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