Possible involvement of Shc in IL-4-induced germline epsilon transcription in a human B cell line.
The IL-4Ralpha contains the I4R motif which binds to the phosphotyrosine binding domain of several adaptor proteins, including IRS-1/2 and Shc. Although the involvement of IRS-1/2 in IL-4-induced PI3-kinase activation is known, there is little information on the role of Shc in IL-4 signaling. In this study, we found the preferential utilization of Shc by the IL-4Ralpha in a human Burkitt's B lymphoma cell line, DND39. IL-4 induced the association of tyrosine-phosphorylated Shc with the IL-4Ralpha, whereas no detectable tyrosine phosphorylation of IRS-1 or IRS-2 was induced. IL-4-induced germline epsilon promoter activation was enhanced by overexpression of Shc and was inhibited by truncated Shc lacking the collagen-homologous domain. We further found the association of Shc with PLCgamma1. Although direct tyrosine phosphorylation of PLCgamma1 was not detectable, the amount of PLCgamma1 coprecipitable with anti-phosphotyrosine was increased after IL-4 stimulation. These results suggest that Shc can function as an adaptor protein of the IL-4Ralpha and mediate the germline epsilon transcription.
Ikizawa
K
K
Clinical Research Center for Allergy, National Sagamihara Hospital, Sagamihara, Kanagawa, 228-8522, Japan. k-ikizawa@taiho.co.jp
Yanagihara
Y
Y
D048868:Adaptor Proteins, Signal Transducing; D033942:Adaptor Proteins, Vesicular Transport; D001402:B-Lymphocytes / Q000187:drug effects / Q000276:immunology* / Q000378:metabolism*; D002051:Burkitt Lymphoma / Q000235:genetics / Q000276:immunology / Q000378:metabolism; D006801:Humans; D055504:Insulin Receptor Substrate Proteins; D015847:Interleukin-4 / Q000378:metabolism / Q000494:pharmacology*; D047908:Intracellular Signaling Peptides and Proteins; D007527:Isoenzymes / Q000378:metabolism; D051966:Phospholipase C gamma; D010750:Phosphoproteins / Q000378:metabolism; D010766:Phosphorylation; D011506:Proteins / Q000737:chemistry / Q000235:genetics / Q000378:metabolism*; D019948:Receptors, Interleukin-4 / Q000378:metabolism; D055765:Shc Signaling Adaptor Proteins; D015398:Signal Transduction; D000071425:Src Homology 2 Domain-Containing, Transforming Protein 1; D014158:Transcription, Genetic / Q000187:drug effects; D014407:Tumor Cells, Cultured; D010738:Type C Phospholipases / Q000378:metabolism; D014443:Tyrosine / Q000378:metabolism
D048868:Adaptor Proteins, Signal Transducing; D033942:Adaptor Proteins, Vesicular Transport; C526292:IRS1 protein, human; C526297:IRS2 protein, human; D055504:Insulin Receptor Substrate Proteins; D047908:Intracellular Signaling Peptides and Proteins; D007527:Isoenzymes; D010750:Phosphoproteins; D011506:Proteins; D019948:Receptors, Interleukin-4; C528024:SHC1 protein, human; D055765:Shc Signaling Adaptor Proteins; D000071425:Src Homology 2 Domain-Containing, Transforming Protein 1; D015847:Interleukin-4; D014443:Tyrosine; D010738:Type C Phospholipases; D051966:Phospholipase C gamma