Insulin selectively activates STAT5b, but not STAT5a, via a JAK2-independent signalling pathway in Kym-1 rhabdomyosarcoma cells.
The STAT multigene family of transcriptional regulators conveys signals from several cytokines and growth factors upon phosphorylation by janus kinases (JAK). Activation of STAT5 is typically mediated by JAK2, but more recent data indicate a direct activation by the insulin receptor kinase. STAT5 exists in two closely homologous isoforms, STAT5a and b. We here describe the selective tyrosine phosphorylation of STAT5b in Kym-1 cells in response to insulin. Blocking insulin signalling by HNMPA-(AM)(3), an insulin receptor kinase inhibitor, resulted in the loss of insulin-induced STAT5b tyrosine phosphorylation, whereas the inhibition of JAK2 by the JAK selective inhibitor tyrphostin AG490 had no effect. By contrast, in the same cells, IFNgamma-induced STAT5b activation was JAK2-dependent, indicating that this signal pathway is functional in Kym-1 cells. We conclude from this rhabdomyosarcoma model that STAT5b, but not STAT5a is a direct target of the insulin receptor kinase.
Storz
P
P
Institute of Cell Biology, University of Stuttgart, Allmandring 31, 70569, Stuttgart, Germany. peter.storz@po.uni-stuttgart.de
Döppler
H
H
Pfizenmaier
K
K
Müller
G
G
D004268:DNA-Binding Proteins / Q000378:metabolism*; D006801:Humans; D007328:Insulin / Q000494:pharmacology*; D053614:Janus Kinase 2; D008894:Milk Proteins; D010766:Phosphorylation; D020033:Protein Isoforms / Q000378:metabolism*; D011505:Protein-Tyrosine Kinases / Q000378:metabolism*; D011518:Proto-Oncogene Proteins; D011972:Receptor, Insulin / Q000378:metabolism; D012208:Rhabdomyosarcoma / Q000201:enzymology / Q000378:metabolism* / Q000473:pathology; D050799:STAT5 Transcription Factor; D015398:Signal Transduction; D015534:Trans-Activators / Q000378:metabolism*; D014407:Tumor Cells, Cultured; D025521:Tumor Suppressor Proteins; D014443:Tyrosine / Q000378:metabolism
D004268:DNA-Binding Proteins; D007328:Insulin; D008894:Milk Proteins; D020033:Protein Isoforms; D011518:Proto-Oncogene Proteins; D050799:STAT5 Transcription Factor; C494092:STAT5A protein, human; C494095:STAT5B protein, human; D015534:Trans-Activators; D025521:Tumor Suppressor Proteins; D014443:Tyrosine; D011505:Protein-Tyrosine Kinases; D011972:Receptor, Insulin; C507924:JAK2 protein, human; D053614:Janus Kinase 2