Interleukin-13 signal transduction in lymphohemopoietic cells. Similarities and differences in signal transduction with interleukin-4 and insulin.
Interleukin-13 (IL-13) and interleukin-4 (IL-4) are related in structure and function and are thought to share a common receptor component. We have investigated the signal transduction pathways activated by these two growth factors, as well as insulin, in cell-lines and primary cells of lymphohemopoietic origin. All three factors induced the ... tyrosine phosphorylation of a protein of 170 kDa (p170), which coimmunoprecipitated with the p85 subunit of P13'-kinase, via high affinity interactions mediated by the SH2 domains of p85. Antibodies raised against the entire insulin-receptor substrate-1 (IRS-1) protein immunoprecipitated p170 much less efficiently than they did IRS-1 from 3T3 cells. However, antibodies directed against the conserved pleckstrin homology domain of IRS-1 immunoprecipitated both p170 and IRS-1 with similar efficiency, suggesting they share structural similarities in this region. In lymphohemopoietic cells, IL-13, IL-4, and insulin failed to induce increased tyrosine phosphorylation of Shc, or its association with grb2, modification of Sos1, or activation of erk-1 and erk-2 mitogen-activated protein kinases, suggesting that p170 mediates downstream pathways distinct from those mediated by IRS-1. Both IL-13 and IL-4 induced low levels of tyrosine phosphorylation of Tyk-2 and Jak-1. IL-4 also activated the Jak-3-kinase, but, despite other similarities, IL-13 did not. Insulin failed to activate any of the known members of the Janus family of kinases. In that Jak-3 is reported to associate with the IL-2 gamma c chain, these data suggest that the IL-13 receptor does not utilize this subunit. However, both IL-13 and IL-4 induced tyrosine phosphorylation of the IL-4-140 kDa receptor chain, suggesting that this is a component of both receptors in these cells and accounts for the similarities in signaling pathways shared by IL-13 and IL-4.
Mesh Terms:
3T3 Cells, Adaptor Proteins, Signal Transducing, Animals, Calcium-Calmodulin-Dependent Protein Kinases, Cells, Cultured, GRB2 Adaptor Protein, Hematopoietic Stem Cells, Humans, Insulin, Insulin Receptor Substrate Proteins, Interleukin-13, Interleukin-13 Receptor alpha1 Subunit, Interleukin-4, Janus Kinase 1, Janus Kinase 3, Leukemia, Erythroblastic, Acute, Lymphocyte Subsets, Mice, Mitogen-Activated Protein Kinase 1, Mitogen-Activated Protein Kinase 3, Mitogen-Activated Protein Kinases, Phosphatidylinositol 3-Kinases, Phosphoproteins, Phosphorylation, Phosphotransferases (Alcohol Group Acceptor), Plasmacytoma, Protein Processing, Post-Translational, Protein-Serine-Threonine Kinases, Protein-Tyrosine Kinases, Proteins, Receptors, Interleukin, Receptors, Interleukin-13, Receptors, Interleukin-4, Recombinant Fusion Proteins, Signal Transduction, Tumor Cells, Cultured
3T3 Cells, Adaptor Proteins, Signal Transducing, Animals, Calcium-Calmodulin-Dependent Protein Kinases, Cells, Cultured, GRB2 Adaptor Protein, Hematopoietic Stem Cells, Humans, Insulin, Insulin Receptor Substrate Proteins, Interleukin-13, Interleukin-13 Receptor alpha1 Subunit, Interleukin-4, Janus Kinase 1, Janus Kinase 3, Leukemia, Erythroblastic, Acute, Lymphocyte Subsets, Mice, Mitogen-Activated Protein Kinase 1, Mitogen-Activated Protein Kinase 3, Mitogen-Activated Protein Kinases, Phosphatidylinositol 3-Kinases, Phosphoproteins, Phosphorylation, Phosphotransferases (Alcohol Group Acceptor), Plasmacytoma, Protein Processing, Post-Translational, Protein-Serine-Threonine Kinases, Protein-Tyrosine Kinases, Proteins, Receptors, Interleukin, Receptors, Interleukin-13, Receptors, Interleukin-4, Recombinant Fusion Proteins, Signal Transduction, Tumor Cells, Cultured
J. Biol. Chem.
Date: May. 19, 1995
PubMed ID: 7744881
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