INTERLEUKIN-3 SIGNALS THROUGH MULTIPLE ISOFORMS OF STAT5

The interleukin (IL)-3 family of cytokines mediates its numerous effec ts on myeloid growth and maturation by binding a family of related rec eptors. It has been shown recently that IL-3 induces the activation of two distinct cytoplasmic signal transducing factors (STFs) that are l ikely to mediate the induction of immediate early genes. In immature m yeloid cells, IL-3 activates STF-IL-3a, which comprises two tyrosine-p hosphorylated DNA binding proteins of 77 and 80 kDa. In mature myeloid cells, IL-3 and granulocyte-macrophage colony-stimulating factor acti vate STF-IL-3b, which consists of a 94 and 96 kDa tyrosine-phosphoryla ted DNA binding protein. Peptide sequence data obtained from the purif ied 77 and 80 kDa proteins (p77 and p80) indicate that they are closel y related but are encoded by distinct genes. Both peptide and nucleoti de sequence data demonstrate that these two proteins are the murine ho mologs of ovine mammary gland factor (MGF)/Stat5. The peptide data als o indicate that p77 and p80 are phosphorylated on tyrosine 699, a posi tion analogous to the tyrosine that is phosphorylated in Stat1 and Sta t2 in response to interferon. Additionally, antiserum raised against b acterially expressed p77/p80 recognizes the 94 and 96 kDa protein comp onents of STF-IL-3b, suggesting that these may be additional isoforms of Stat5. These studies indicate that the IL-3 family of ligands is ab le to activate multiple isoforms of the signal transducing protein Sta t5.