Cytokines Pathway

Abstract

An important group of signalling molecules operate through a pathway which is slightly different from that described in Chap. 1: their receptors do not present tyrosine kinase activity but are coupled to a cytoplasmic tyrosine kinase which ensures, after receptor activation, the transduction of a signal leading to the transcription of target genes. The main signalling pathway downstream the activation of these receptors by their ligands involves cytoplasmic JAK (just another kinase, now Janus kinase) proteins and STAT (signal transducer and activator of transcription) transcription factors, but the activation of other kinases is sometimes possible, with connections with the MAP kinases (Chap. 2) and the PI3 kinase (Chap. 3) pathways.

Whereas the word ‘cytokine’ designates often a large variety of signalling proteins, including growth factors (Chap. 1), TNF-related factors and chemokines (Chap. 6), we will adopt a mechanistic definition and restrict this denomination to the ligands of membrane receptors devoid of tyrosine kinase activity but coupled with cytoplasmic tyrosine kinases. This includes most interleukins and interferons, but excludes many signalling molecules that activate other receptors, such as tyrosine kinase receptors, death receptors, interleukin-1 and toll-like receptors, etc. The cytokines envisaged in this chapter may be involved in multiple cell processes: proliferation and differentiation of blood cells, immunity and inflammation, body weight and size control, antiviral defences, etc.