IRS-1: essential for insulin- and IL-4-stimulated mitogenesis in hematopoietic cells.

Although several interleukin-3 (IL-3)-dependent cell lines proliferate in response to IL-4 or insulin, the 32D line does not. Insulin and IL-4 sensitivity was restored to 32D cells by expression of IRS-1, the principal substrate of the insulin receptor. Although 32D cells possessed receptors for both factors, they lacked the IRS-1--related protein, 4PS, which becomes phosphorylated by tyrosine in insulin- or IL-4--responsive lines after stimulation. These results indicate that factors that bind unrelated receptors can use similar mitogenic signaling pathways in hematopoietic cells and that 4PS and IRS-1 are functionally similar proteins that are essential for insulin- and IL-4--induced proliferation.

[1]  A. Ullrich,et al.  The SH2/SH3 domain‐containing protein GRB2 interacts with tyrosine‐phosphorylated IRS1 and Shc: implications for insulin control of ras signalling. , 1993, The EMBO journal.

[2]  G. Lienhard,et al.  Common elements in interleukin 4 and insulin signaling pathways in factor-dependent hematopoietic cells. , 1993, Proceedings of the National Academy of Sciences of the United States of America.

[3]  R. Aebersold,et al.  The insulin-elicited 160 kDa phosphotyrosine protein in mouse adipocytes is an insulin receptor substrate 1: identification by cloning. , 1993, Biochimica et biophysica acta.

[4]  J. Gutkind,et al.  IL‐4 activates a distinct signal transduction cascade from IL‐3 in factor‐dependent myeloid cells. , 1992, The EMBO journal.

[5]  B. Neel,et al.  Identification of a human src homology 2-containing protein-tyrosine-phosphatase: a putative homolog of Drosophila corkscrew. , 1992, Proceedings of the National Academy of Sciences of the United States of America.

[6]  C. Kahn,et al.  Expression and function of IRS-1 in insulin signal transmission. , 1992, The Journal of biological chemistry.

[7]  M. White,et al.  IRS-1 activates phosphatidylinositol 3'-kinase by associating with src homology 2 domains of p85. , 1992, Proceedings of the National Academy of Sciences of the United States of America.

[8]  B. Margolis,et al.  Phosphatidylinositol 3′‐kinase is activated by association with IRS‐1 during insulin stimulation. , 1992, The EMBO journal.

[9]  A. Ullrich,et al.  The SH2 and SH3 domain-containing protein GRB2 links receptor tyrosine kinases to ras signaling , 1992, Cell.

[10]  V. Duronio,et al.  p21ras activation via hemopoietin receptors and c-kit requires tyrosine kinase activity but not tyrosine phosphorylation of p21ras GTPase-activating protein. , 1992, Proceedings of the National Academy of Sciences of the United States of America.

[11]  J. McCubrey,et al.  Growth-promoting effects of insulin-like growth factor-1 (IGF-1) on hematopoietic cells: overexpression of introduced IGF-1 receptor abrogates interleukin-3 dependency of murine factor-dependent cells by a ligand-dependent mechanism , 1991 .

[12]  C. Kahn,et al.  Structure of the insulin receptor substrate IRS-1 defines a unique signal transduction protein , 1991, Nature.

[13]  A. Ullrich,et al.  Cytoplasmic juxtamembrane region of the insulin receptor: a critical role in ATP binding, endogenous substrate phosphorylation, and insulin-stimulated bioeffects in CHO cells. , 1991, Biochemistry.

[14]  M. Nakafuku,et al.  Involvement of ras p21 protein in signal-transduction pathways from interleukin 2, interleukin 3, and granulocyte/macrophage colony-stimulating factor, but not from interleukin 4. , 1991, Proceedings of the National Academy of Sciences of the United States of America.

[15]  J B Gibbs,et al.  Modulation of guanine nucleotides bound to Ras in NIH3T3 cells by oncogenes, growth factors, and the GTPase activating protein (GAP). , 1990, The Journal of biological chemistry.

[16]  A. Ullrich,et al.  Receptor-mediated internalization of insulin requires a 12-amino acid sequence in the juxtamembrane region of the insulin receptor beta-subunit. , 1990, The Journal of biological chemistry.

[17]  J. Banchereau,et al.  Molecular cloning of a cDNA encoding the human interleukin 4 receptor. , 1990, International immunology.

[18]  Alan I. Alpert,et al.  The murine interleukin-4 receptor: Molecular cloning and characterization of secreted and membrane bound forms , 1989, Cell.

[19]  A. Ullrich,et al.  Mutation of the insulin receptor at tyrosine 960 inhibits signal transmission but does not affect its tyrosine kinase activity , 1988, Cell.

[20]  J. Schlessinger,et al.  Signal transduction through the EGF receptor transfected in IL-3-dependent hematopoietic cells. , 1988, Science.

[21]  J. Lowenthal,et al.  Expression of high affinity receptors for murine interleukin 4 (BSF-1) on hemopoietic and nonhemopoietic cells. , 1988, Journal of immunology.

[22]  A. Ullrich,et al.  Overexpression of the human EGF receptor confers an EGF-dependent transformed phenotype to NIH 3T3 cells , 1987, Cell.

[23]  A. Ullrich,et al.  Human insulin receptors mutated at the ATP-binding site lack protein tyrosine kinase activity and fail to mediate postreceptor effects of insulin. , 1987, The Journal of biological chemistry.

[24]  J. Watson,et al.  Induction of IL 2 responsiveness in a murine IL 3-dependent cell line. , 1985, Journal of immunology.

[25]  C. Kahn,et al.  Insulin rapidly stimulates tyrosine phosphorylation of a Mr-185,000 protein in intact cells , 1985, Nature.

[26]  C. Kahn,et al.  Insulin stimulates the phosphorylation of the 95,000-dalton subunit of its own receptor. , 1982, Science.

[27]  E. Scolnick,et al.  Growth of factor-dependent hemopoietic precursor cell lines , 1980, The Journal of experimental medicine.