STATs are proteins with a dual function: signal transducers in the cytoplasm and transcriptional activators in the nucleus. Among the six Known major STATs (STAT1-6), STAT3 has been implicated in the widest range of signaling pathways that regulate cell growth and differentiation. As a part of our on-going investigation on the pleiotropic functions of STAT proteins, we examined the role of STAT3 as a molecular adaptor that links diverse cell growth signaling pathways. We observed that STAT3 can be specifically activated by multiple cytokines, such as IL-3, in transformed fibroblasts and IL-4 or IFN-γ in primary immune cells, respectively. The selective activation of STAT3 in H-ras-transformed NIH3T3 cells is associated with an increased expression of phosphoserine STAT3 in these cells, compared to the parental cells. Notably phosphoresine-STAT3 interacts with oncogenic ras, shown by immunoprecipitation and Western blots. The results suggest the role of STAT3 in rasinduced cellular transformation as a molecular adaptor linking the Jak/STAT and Ras/MAPK pathways. In primary immune cells, IL-4 and IFN-γ each induced (in addition to the characteristic STATE and STAT1 homodimers) the formation of STAT3-containing complexes that bind to GAS probes, which correspond to the FcE RII and Fcy RI promoter sequences, respectively Since IL-4 and IFN-γ are known to counter-regulate the expression of these genes, the ability of STAT3 to form heterodimeric complexes with STATE or STAT1 implies its role in the one-tuned control of genes that are regulated by IL-4 and IFN-γ.