cDNA cloning and functional analysis of a truncated STAT5a protein from autonomously growing FDCP-1 cells

The transcription factor STAT5 is activated by multiple hematopoietic cytok ine receptors and has been implicated in the induction of cellular processe s such as differentiation, proliferation and antiapoptotic activities. Here , we report cloning of the cDNA and characterization of a mutant STAT5a pro tein that is expressed in interleukin-3 (IL3)-independently growing FDCP-1 cells. Analysis of the cDNA revealed a deletion of both the transactivation and the SH2 domains. Stable expression of the protein in parental IL-3-dep endent cells results in elevated DNA binding activity of wild type (WT)-STA T5 in the nucleus, enhanced growth rates and a reduced susceptibility to un dergo apoptosis after withdrawal of IL-3. Although the protein is not prese nt in DNA/protein complexes in the nucleus, we observed pronounced effects on IL-3-induced signal transduction. The results suggest competition of the mutant protein with cytosolic mechanisms regulating STAT5 activity. In con clusion, the data support the hypothesis of an involvement of STAT5 in mito genic and antiapoptotic signaling. (C) 2000 Elsevier Science Inc. All right s reserved.