Differential phosphorylation of Janus kinase 2, Stat5A and Stat5B in response to growth hormone in primary rat adipocytes.
In vitro growth hormone (GH) stimulation of Janus kinase 2 (Jak2) tyrosine phosphorylation and activation has been detected in rat adipocytes where GH exerts both chronic diabetogenic and acute insulin-like effects but not in adipocytes where only chronic diabetogenic effects are exerted. The 95 kDa transcription factor Stat5, which is tyrosine phosphorylated in response to GH in both cases, is here identified as the 5A-isoform. Stat5B was not tyrosine phosphorylated in response to GH in adipocytes but subject to a gel supershift indicating regulation by serine and/or threonine phosphorylation. The differential tyrosine phosphorylation of these proteins suggests involvement of a kinase other than Jak2 in Stat5A activation. However, in adipocytes where GH exerts both diabetogenic and insulin-like effects, and both Jak2 and Stat5A were activated, their phosphorylation kinetics and downregulation of tyrosine phosphorylation were almost identical. We conclude that Stat5A is important for the diabetogenic actions of GH and that Jak2 still is the most probable candidate kinase for Stat5A in primary adipocytes.
Ridderstråle
M
M
Department of Endocrinology, Lund University, Wallenberglaboratory, University Hospital Malmö, S-205 02 Malmo, Sweden. martin.ridderstrale@endo.mas.lu.se
Groop
L
L
D017667:Adipocytes / Q000187:drug effects* / Q000378:metabolism; D000818:Animals; D002478:Cells, Cultured; D004268:DNA-Binding Proteins / Q000378:metabolism*; D013006:Growth Hormone / Q000494:pharmacology*; D006801:Humans; D053614:Janus Kinase 2; D008297:Male; D008894:Milk Proteins; D010766:Phosphorylation; D020033:Protein Isoforms; D011505:Protein-Tyrosine Kinases / Q000378:metabolism*; D011518:Proto-Oncogene Proteins; D051381:Rats; D017207:Rats, Sprague-Dawley; D011994:Recombinant Proteins / Q000378:metabolism; D050799:STAT5 Transcription Factor; D015398:Signal Transduction / Q000502:physiology; D015534:Trans-Activators / Q000378:metabolism*; D025521:Tumor Suppressor Proteins
D004268:DNA-Binding Proteins; D008894:Milk Proteins; D020033:Protein Isoforms; D011518:Proto-Oncogene Proteins; D011994:Recombinant Proteins; D050799:STAT5 Transcription Factor; C494092:STAT5A protein, human; C494095:STAT5B protein, human; C494094:Stat5a protein, rat; C494097:Stat5b protein, rat; D015534:Trans-Activators; D025521:Tumor Suppressor Proteins; D013006:Growth Hormone; D011505:Protein-Tyrosine Kinases; C507924:JAK2 protein, human; C507927:Jak2 protein, rat; D053614:Janus Kinase 2