Nongenomic functions of STAT3

STAT3 was discovered as a transcription factor activated during inflammatory cytokine signaling, largely through the action of cytokines that utilize receptors that engage the gp130 signal transducer. While the paradigm of receptor-dependent protein tyrosine phosphorylation of STAT3 has explained many of the biological activities ascribed to this protein, additional functions have been discovered in recent years. These functions involve actions of STAT3 outside the nucleus and do not rely on its ability to interact with chromatin and trigger gene expression. Nongenomic functions of STAT3 include action in the cell cytoplasm and in mitochondria, where it impacts metabolic activities involved in a diverse set of cell functions, including malignant transformation.