Jak2 tyrosine kinase: a mediator of both housekeeping and ligand-dependent gene expression?

Jak2 is a nonreceptor tyrosine kinase that is essential for proper animal development and physiology. It is activated by ligand-occupied cell-surface receptors. Once activated, it then tyrosine phosphorylates the latent cytoplasmic transcription factors, termed the signal transducers and activators of transcription (STAT) proteins. Thus Jak2 is viewed as a classic mediator of ligand-dependent signal transduction. Recent studies, however, suggest that Jak2 may mediate cellular gene expression outside of the classically defined, ligand-activated, Jak/STAT-signaling paradigm. Here we review these studies, provide additional data, and discuss whether Jak2 is a mediator of ligand-independent gene transcription, and, in turn, whether our current understanding of the Jak/STAT signaling paradigm should be modified to incorporate these observations.