Abstract
Insulin receptor substrate 1 (IRS-1), and its structural relative IRS-2, are both phosphorylated on tyrosine following treatment of cells with interleukin-4 (IL-4) and insulin. We have investigated whether both IRS-1 and IRS-2 are expressed in murine lymphohemopoietic cells. T and B lymphocytes and macrophages from primary cultures expressed only IRS-2, which became phosphorylated on tyrosine following stimulation with both IL-4 and insulin. Likewise, the murine myeloid cell line FD-5 expressed only IRS-2, which was tyrosine phosphorylated in response to IL-4 and insulin, as well as interleukin-3 and granulocyte-macrophage colony stimulating factor. Neither IRS-1 nor IRS-2 were expressed at detectable levels in primary bone marrow mast cells although these cells do respond to IL-4. Moreover, a factor-dependent lymphocyte cell line, CT.4S, which grows continuously in IL-4, did not express detectable levels of IRS-1 or IRS-2. IRS-2 from FD-5 cells stimulated with either IL-4 or insulin bound to glutathione S-transferase fusion proteins of the p85 subunit of phosphoinositol 3'-kinase, Grb2, and Syp, paralleling reported associations of IRS-1 with these molecules and indicating phosphorylation of the corresponding residues on IRS-2.
Publication types
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Research Support, Non-U.S. Gov't
MeSH terms
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Adaptor Proteins, Signal Transducing*
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Animals
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Avian Proteins*
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Cytokines / pharmacology*
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Cytoskeletal Proteins / metabolism
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ErbB Receptors / metabolism
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GRB2 Adaptor Protein
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Granulocyte-Macrophage Colony-Stimulating Factor / pharmacology
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Hematopoietic Stem Cells / metabolism*
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Insulin / pharmacology
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Insulin Receptor Substrate Proteins
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Interleukin-3 / pharmacology
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Interleukin-4 / pharmacology
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Intracellular Signaling Peptides and Proteins
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Lymphocytes / metabolism*
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Mice
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Molecular Weight
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Phosphoproteins / metabolism*
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Phosphorylation
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Protein Tyrosine Phosphatase, Non-Receptor Type 11
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Protein Tyrosine Phosphatase, Non-Receptor Type 6
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Protein Tyrosine Phosphatases / metabolism
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Proteins / metabolism
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Tyrosine / metabolism*
Substances
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Adaptor Proteins, Signal Transducing
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Avian Proteins
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Cytokines
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Cytoskeletal Proteins
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GRB2 Adaptor Protein
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Grb2 protein, mouse
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Insulin
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Insulin Receptor Substrate Proteins
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Interleukin-3
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Intracellular Signaling Peptides and Proteins
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Irs1 protein, mouse
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Irs2 protein, mouse
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Phosphoproteins
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Proteins
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cytoskeletal p85 protein, chicken
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Interleukin-4
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Tyrosine
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Granulocyte-Macrophage Colony-Stimulating Factor
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ErbB Receptors
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Protein Tyrosine Phosphatase, Non-Receptor Type 11
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Protein Tyrosine Phosphatase, Non-Receptor Type 6
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Protein Tyrosine Phosphatases
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Ptpn11 protein, mouse
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Ptpn6 protein, mouse