Figure 1

Role of STATs in cell stress responses. (A) Autocrine IFN may activate JAK/STAT through the canonical pathway. This activation would involve tyrosine phosphorylation of STAT by JAK resulting in STAT dimers which are 20% transcriptionally active. This process is thought to "prime" STATs for serine phosphorylation by an IFN-inducible serine kinase (possibly PKC) [42]. Both tyrosine and serine phosphorylation results in a 100% transcriptionally active STAT1 dimer. (B) Hypoxia-reperfusion injury may directly activate p38 MAPK which phosphorylates STAT1 on SER727. Serine phosphorylated STAT could then participate in protein-protein interactions with other STAT binding proteins and activate the expression of pro-apoptotic genes like FAS. (C) In this case, hypoxia-reperfusion may activate STAT5 resulting in activation of cell survival pathways. STAT5 activation by hypoxia may be mediated by JAK2 and a STAT5/cSrc/PI-3 kinase/Akt pathway. (D) STAT3 may act as a constitutive FAS repressor, but FAS is de-repressed during UV stress which may involve STAT3 inhibition by PI3-kinase/Akt.