Constitutive association of JAK1 and STAT5 in pro-B cells is dissolved by interleukin-4-induced tyrosine phosphorylation of both proteins.
The bipartite human interleukin-4 (IL-4) receptor was functionally expressed in murine pro-B cells and activated by human IL-4 to evoke intracellular signaling. Mutual association of signal transducing proteins within the receptor complex was then studied in dependence of ligand stimulation. Besides ligand-induced receptor heterodimerization and contacts of the two IL-4 receptor subunits alpha and gamma with Janus kinases JAK1 and JAK3 a prominent constitutive binding between JAK1 and signal transducer and activator of transcription STAT5 was detected. Since both these proteins become phosphorylated in response to IL-4 receptor stimulation, the influence of tyrosine phosphorylation on their mutual contact was analyzed. Association of JAK1 and STAT5 was found to occur exclusively between unphosphorylated proteins.
Erhardt
I
I
Theodor-Boveri-Institut für Biowissenschaften (Biozentrum), Physiologische Chemie II, Am Hubland, Würzburg, Germany.
Lischke
A
A
Sebald
W
W
Friedrich
K
K
D001402:B-Lymphocytes / Q000187:drug effects / Q000201:enzymology / Q000378:metabolism*; D002460:Cell Line; D004268:DNA-Binding Proteins / Q000378:metabolism*; D006801:Humans; D015847:Interleukin-4 / Q000494:pharmacology*; D053613:Janus Kinase 1; D008894:Milk Proteins; D010766:Phosphorylation / Q000187:drug effects; D011505:Protein-Tyrosine Kinases / Q000378:metabolism*; D018121:Receptors, Cytokine / Q000378:metabolism; D050799:STAT5 Transcription Factor; D015534:Trans-Activators / Q000378:metabolism*; D014443:Tyrosine / Q000378:metabolism
D004268:DNA-Binding Proteins; D008894:Milk Proteins; D018121:Receptors, Cytokine; D050799:STAT5 Transcription Factor; D015534:Trans-Activators; D015847:Interleukin-4; D014443:Tyrosine; D011505:Protein-Tyrosine Kinases; C507904:JAK1 protein, human; D053613:Janus Kinase 1