Cytoplasmic STAT proteins associate prior to activation

The commonly accepted model of STAT factor activation at the cytoplasmic pa rt of the receptor assumes that signal transducers and activators of transc ription (STATs) are recruited from a cytoplasmic pool of monomeric STAT pro teins. Based on a previous observation that non-phosphorylated STAT3-Src ho mology 2 domains dimerize in vitro, we investigated whether the observed di merization is of physiological relevance within the cellular context. We sh ow that STAT1 and STAT3 are pre-associated in non-stimulated cells. Apparen tly, these complexes are not able to translocate into the nucleus. We provi de evidence that the event of STAT activation is more complex than previous ly assumed.