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 lymphohemopo...

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Veröffentlicht in:The Journal of biological chemistry 1995-05, Vol.270 (20), p.12286-12296
Hauptverfasser: Welham, M J, Learmonth, L, Bone, H, Schrader, J W
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container_issue 20
container_start_page 12286
container_title The Journal of biological chemistry
container_volume 270
creator Welham, M J
Learmonth, L
Bone, H
Schrader, J W
description 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.
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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. 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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.</abstract><cop>United States</cop><pmid>7744881</pmid><doi>10.1074/jbc.270.20.12286</doi><tpages>11</tpages></addata></record>
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subjects 3T3 Cells - metabolism
Adaptor Proteins, Signal Transducing
Animals
Calcium-Calmodulin-Dependent Protein Kinases - metabolism
Cells, Cultured
GRB2 Adaptor Protein
Hematopoietic Stem Cells - drug effects
Hematopoietic Stem Cells - physiology
Humans
Insulin - pharmacology
Insulin Receptor Substrate Proteins
Interleukin-13 - pharmacology
Interleukin-13 Receptor alpha1 Subunit
Interleukin-4 - pharmacology
Janus Kinase 1
Janus Kinase 3
Leukemia, Erythroblastic, Acute - pathology
Lymphocyte Subsets - drug effects
Lymphocyte Subsets - physiology
Mice
Mitogen-Activated Protein Kinase 1
Mitogen-Activated Protein Kinase 3
Mitogen-Activated Protein Kinases
Phosphatidylinositol 3-Kinases
Phosphoproteins - immunology
Phosphoproteins - metabolism
Phosphoproteins - physiology
Phosphorylation
Phosphotransferases (Alcohol Group Acceptor) - metabolism
Plasmacytoma - pathology
Protein Processing, Post-Translational - drug effects
Protein-Serine-Threonine Kinases - metabolism
Protein-Tyrosine Kinases - metabolism
Proteins - genetics
Proteins - metabolism
Receptors, Interleukin - drug effects
Receptors, Interleukin - physiology
Receptors, Interleukin-13
Receptors, Interleukin-4
Recombinant Fusion Proteins - metabolism
Signal Transduction - drug effects
Tumor Cells, Cultured
title Interleukin-13 signal transduction in lymphohemopoietic cells. Similarities and differences in signal transduction with interleukin-4 and insulin
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