Emancipation from transcriptional latency: unphosphorylated STAT5 as guardian of hematopoietic differentiation

Abstract

The canonical paradigm of Jak–STAT signal-ing is that members of the signal transduc-ers and activators of transcription (STATs) family of transcription factors are activated by Janus kinase (Jak)-mediated tyrosine phosphorylation. While the relationship between activation and tyrosine phospho-rylation still appears axiomatic, several lines of evidence suggest that unactivated, unphosphorylated isoforms, uSTATs, are nonetheless also engaged in transcriptional regulation. In this issue of The EMBO Jour-nal, Park et al (2016) make a convincing case that nuclear uSTAT5 controls hematopoietic differentiation.