Interleukin-4 (IL-4) induces phosphatidylinositol 3-kinase (p85) dephosphorylation. Implications for the role of SHP-1 in the IL-4-induced signals in human B cells.
Interleukin 4 (IL-4) is a potent cytokine produced by T cells and to a lesser extent by tumor-associated natural killer cells, basophils, and mast cells. IL-4 treatment of T cells and macrophages leads to augmentation of their cytotoxic activity. In human B cells, IL-4 is a potent stimulator of Ig class switching from IgM to IgE. The diverse biological responses induced by IL-4 are mediated through a high affinity receptor complex (IL-4R). Although a wealth of information has accumulated regarding IL-4R, the exact mechanisms of IL-4R-mediated signaling pathways in human B cells are not well defined. In an attempt to characterize the IL-4-induced signals in human B cells, we have found that IL-4 treatment induced rapid dephosphorylation of the 85-kDa regulatory subunit of phosphatidylinositol 3-kinase. To identify the protein-tyrosine phosphatase involved in the IL-4-mediated dephosphorylation, we performed Western blot analysis using monoclonal antibodies specific to protein-tyrosine phosphatases. Upon IL-4 treatment, SHP-1 was specifically translocated to the cellular membrane fraction. Furthermore, immunoprecipitation studies revealed that SHP-1 could be specifically coimmunoprecipitated with the IL-4R as well as with phosphatidylinositol 3-kinase (p85). Collectively, our observations suggest that in addition to protein phosphorylation, protein tyrosine dephosphorylation may play a role in the IL-4-induced signaling pathways.
Imani
F
F
Department of Medicine, The Johns Hopkins University School of Medicine, Asthma and Allergy Center, Baltimore, Maryland 21224, USA.
Rager
K J
KJ
Catipovic
B
B
Marsh
D G
DG
D015703:Antigens, CD / Q000378:metabolism; D001402:B-Lymphocytes / Q000378:metabolism*; D001692:Biological Transport; D002462:Cell Membrane / Q000378:metabolism; D006801:Humans; D015847:Interleukin-4 / Q000494:pharmacology*; D047908:Intracellular Signaling Peptides and Proteins; D007700:Kinetics; D019869:Phosphatidylinositol 3-Kinases; D010766:Phosphorylation; D017853:Phosphotransferases (Alcohol Group Acceptor) / Q000378:metabolism*; D011485:Protein Binding; D054592:Protein Tyrosine Phosphatase, Non-Receptor Type 11; D053824:Protein Tyrosine Phosphatase, Non-Receptor Type 6; D017027:Protein Tyrosine Phosphatases / Q000378:metabolism*; D018123:Receptors, Interleukin / Q000378:metabolism; D019948:Receptors, Interleukin-4; D011994:Recombinant Proteins / Q000494:pharmacology; D015398:Signal Transduction; D014407:Tumor Cells, Cultured; D014443:Tyrosine / Q000378:metabolism
D015703:Antigens, CD; D047908:Intracellular Signaling Peptides and Proteins; D018123:Receptors, Interleukin; D019948:Receptors, Interleukin-4; D011994:Recombinant Proteins; D015847:Interleukin-4; D014443:Tyrosine; D019869:Phosphatidylinositol 3-Kinases; D017853:Phosphotransferases (Alcohol Group Acceptor); C516724:PTPN11 protein, human; C509249:PTPN6 protein, human; D054592:Protein Tyrosine Phosphatase, Non-Receptor Type 11; D053824:Protein Tyrosine Phosphatase, Non-Receptor Type 6; D017027:Protein Tyrosine Phosphatases