Positive Regulators of the Jak/STAT Pathway

The Jak/STAT pathway is critical for many processes including hematopoiesis, immune cell development, and inflammatory responses. This pathway is relatively basic as its main components are only Jak tyrosine kinases and STAT transcription factors. However, the pathway utilizes additional effectors to promote Jak/STAT signaling. For example, a number of proteins, such as SH2B1 and STI1, associate with and facilitate the activity of Jak proteins. Additionally, STAT proteins can interact with cofactors and cooperating transcription factors, thereby enhancing their transcriptionally activity. STAT activity is also regulated by several serine/threonine intracellular kinases. STAT proteins, except STAT2, contain at least one conserved serine phosphorylation site in their transcriptional activation domain. It is thought that serine phosphorylation of STAT proteins dramatically enhances STAT-mediated gene expression.