JAK3 associates with the human interleukin 4 receptor and is tyrosine phosphorylated following receptor triggering.
In human B cells, interleukin 4 (IL4) acts in regulating proliferation, antigen expression, isotype switching and differentiation. These different effects are mediated through the IL4R complex including the IL2R gamma chain (gamma c) and a specific p130/140 binding unit referred below as human Interleukin 4 Receptor (IL4-R). Here, we studied the signal transduction events following IL4R activation and leading to CD23 expression on resting B cells. We demonstrate that IL4R triggering induced the tyrosine phosphorylation of JAK3 and of a p170 protein. Coimmunoprecipitation of JAK3 with the IL4R suggests a physical association which exists prior to IL4R complex stimulation. Orthovanadate treatment, while having no effect on IL4-induced p130 phosphorylation, leads to the hyperphosphorylation of the p170 and inhibits IL4-induced CD23 expression. These suggest that two mandatory steps exist in early IL4 signaling: one controlled by JAK3 activation and the other by the p170 phosphoprotein.
Rolling
C
C
INSERM U131, Institut Paris-Sud sur les Cytokines, Clamart, France.
Treton
D
D
Beckmann
P
P
Galanaud
P
P
Richard
Y
Y
D001402:B-Lymphocytes / Q000378:metabolism*; D002648:Child; D006801:Humans; D015847:Interleukin-4 / Q000494:pharmacology; D053614:Janus Kinase 2; D053616:Janus Kinase 3; D008213:Lymphocyte Activation; D014066:Palatine Tonsil; D010766:Phosphorylation; D019000:Phosphotyrosine; D011505:Protein-Tyrosine Kinases / Q000378:metabolism*; D011518:Proto-Oncogene Proteins; D018123:Receptors, Interleukin / Q000378:metabolism*; D019948:Receptors, Interleukin-4; D015398:Signal Transduction; D014443:Tyrosine / Q000031:analogs & derivatives / Q000378:metabolism
D011518:Proto-Oncogene Proteins; D018123:Receptors, Interleukin; D019948:Receptors, Interleukin-4; D015847:Interleukin-4; D019000:Phosphotyrosine; D014443:Tyrosine; D011505:Protein-Tyrosine Kinases; C507924:JAK2 protein, human; C507933:JAK3 protein, human; D053614:Janus Kinase 2; D053616:Janus Kinase 3