The Jak–STAT pathway: specific signal transduction from the cell membrane to the nucleus

Abstract

The Jak-STAT pathway is a newly discovered intracellular signal transduction pathway that is used by a growing number of extracellular signalling proteins (ESPs) for transcriptional activation of target genes. Binding of ligands to their transmembrane receptors leads to activation of members of the Jak tyrosine kinase family. The activated receptor-kinase complexes recruit members of the STAT family and activate them by phosphorylation. As a consequence, the phosphorylated STAT proteins dimerize, translocate into the nucleus, bind response elements in the promoter of target genes and stimulate the transcription of these genes. Their dual role as signalling molecules and transcription factors is reflected in the name: STAT stands for Signal Transducers and Activators of Transcription. Different ligands specifically activate different members of the Jak and STAT families. Signal transduction through the Jak-STAT pathway contributes to the specificity and diversity of cellular responses to peptide hormones, growth factors, cytokines and interleukins.