Fig. 1

Cytokine-induced STAT activation. (A) STATs are latent transcription factors found in the cytoplasm of cells. (B) When a cytokine interacts with its cell surface receptor, it induces receptor dimerization, bringing into juxtaposition associated Jak family tyrosine kinases. The Jaks become activated, leading to the tyrosine phosphorylation of themselves and the associated receptor chains. STATs are recruited to the activated kinase-receptor complex, where they become phosphorylated on unique tyrosine residues. (C) Once tyrosine is phosphorylated, the STATs dimerize, translocate to the nucleus, and bind to specific DNA sequences in the regulatory regions of target genes where they can modulate transcription. (D) STATs can also be phosphorylated on specific serine residues. Although this is not sufficient to activate the STATs, it leads to an enhancement of the transcriptional response mediated by tyrosine-phosphorylated STATs.