Functionally distinct isoforms of STAT5 are generated by protein processing.
The interleukin-3 family of cytokines, which play an important role in the development of myeloid lineages, transduce signals through the JAK-STAT pathway. Previous studies demonstrate that this process entails the activation of four distinct isoforms of STAT5, where two shorter isoforms are activated in a distinct population of cells. We now demonstrate that the shorter isoforms represent carboxy-terminal truncations. Moreover, these truncations are not generated by RNA processing, but by a specific proteolytic activity. Consistent with the notion that truncated STAT5 isoforms transduce distinct signals, they fail to promote the activation of several known interleukin-3 target genes. These studies suggest that the activity of a specific protease may play a critical role in defining the biological responses transduced by STAT5.
Azam
M
M
Department of Medicine, College of Physicians and Surgeons, Columbia University, New York, New York 10032, USA.
Lee
C
C
Strehlow
I
I
Schindler
C
C
D002478:Cells, Cultured; D004268:DNA-Binding Proteins / Q000737:chemistry* / Q000378:metabolism; D005786:Gene Expression Regulation; D006801:Humans; D007377:Interleukin-3 / Q000235:genetics / Q000502:physiology; D008894:Milk Proteins; D008970:Molecular Weight; D011499:Protein Processing, Post-Translational; D012323:RNA Processing, Post-Transcriptional; D012333:RNA, Messenger / Q000235:genetics; D050799:STAT5 Transcription Factor; D015398:Signal Transduction; D013329:Structure-Activity Relationship; D015534:Trans-Activators / Q000737:chemistry* / Q000378:metabolism
D004268:DNA-Binding Proteins; D007377:Interleukin-3; D008894:Milk Proteins; D012333:RNA, Messenger; D050799:STAT5 Transcription Factor; D015534:Trans-Activators