Differential effects of prolactin and src/abl kinases on the nuclear translocation of STAT5B and STAT5A.
In this study, DNA binding and tyrosine phosphorylation of STAT5A and STAT5B were compared with their subcellular localization determined using indirect immunofluorescence microscopy. Following prolactin activation, both STAT5A and STAT5B were rapidly translocated into the nucleus and displayed a detergent-resistant, punctate nuclear staining pattern. Similar to prolactin induction, src activation resulted in tyrosine phosphorylation and DNA binding of both STAT5A and STAT5B. However, nuclear translocation of only STAT5B but not STAT5A was observed. This selective nuclear translocation appears to be mediated via the carboxyl-terminal sequences in STAT5B. Furthermore, overexpression of a dominant negative kinase-inactive mutant of JAK2 prevented prolactin-induced tyrosine phosphorylation and nuclear translocation of STAT5A and STAT5B but did not block src kinase activation and nuclear translocation of STAT5B. In co-transfection assays, prolactin-mediated activation but not src kinase-mediated activation of STAT5B resulted in the induction of a beta-casein promoter-driven reporter construct. These results suggest that STAT5 activation by src may occur by a mechanism distinct from that employed in cytokine activation of the JAK/STAT pathway, resulting in the selective nuclear translocation of STAT5B.
Kazansky
A V
AV
Department of Cell Biology, Baylor College of Medicine, Houston, Texas 77030-3498, USA.
Kabotyanski
E B
EB
Wyszomierski
S L
SL
Mancini
M A
MA
Rosen
J M
JM
D000595:Amino Acid Sequence; D001692:Biological Transport / Q000187:drug effects; D002364:Caseins / Q000235:genetics; D002451:Cell Compartmentation; D002467:Cell Nucleus / Q000378:metabolism*; D003593:Cytoplasm / Q000378:metabolism; D004268:DNA-Binding Proteins / Q000235:genetics / Q000378:metabolism*; D004789:Enzyme Activation; D019084:Fluorescent Antibody Technique, Indirect; D017930:Genes, Reporter; D053614:Janus Kinase 2; D008894:Milk Proteins; D008954:Models, Biological; D008969:Molecular Sequence Data; D010766:Phosphorylation; D011388:Prolactin / Q000494:pharmacology*; D011485:Protein Binding; D011505:Protein-Tyrosine Kinases / Q000378:metabolism*; D011518:Proto-Oncogene Proteins; D016315:Proto-Oncogene Proteins c-abl / Q000378:metabolism; D011981:Receptors, Prolactin / Q000378:metabolism*; D011994:Recombinant Proteins / Q000378:metabolism; D050799:STAT5 Transcription Factor; D015534:Trans-Activators / Q000235:genetics / Q000378:metabolism*; D015533:Transcriptional Activation; D019061:src-Family Kinases / Q000378:metabolism
D002364:Caseins; D004268:DNA-Binding Proteins; D008894:Milk Proteins; D011518:Proto-Oncogene Proteins; D011981:Receptors, Prolactin; D011994:Recombinant Proteins; D050799:STAT5 Transcription Factor; D015534:Trans-Activators; D011388:Prolactin; D011505:Protein-Tyrosine Kinases; D053614:Janus Kinase 2; D016315:Proto-Oncogene Proteins c-abl; D019061:src-Family Kinases