Common Elements in Interleukin 4 and Insulin Signaling Pathways in Factor- Dependent Hematopoietic Cells

• Published in: Proceedings of the National Academy of Sciences - PNAS 1993-05, Vol.90 (9), p.4032-4036
• Main Authors: Wang, Ling-Mei, Keegan, Achsah D., Li, Weiqun, Lienhard, Gustav E., Pacini, Stefania, Gutkind, J. Silvio, Myers, Martin G., Sun, Xiao-Jian, White, Morris F., Aaronson, Stuart A., Paul, William E., Pierce, Jacalyn H.
• Format: Article
• Language: English
• Subjects: Animals; B lymphocytes; Biological and medical sciences; Blood Cells; Cell Division - drug effects; Cell growth; Cell Line; Cell lines; Cell physiology; Cells; Cellular biology; CHO Cells; Cricetinae; Culture Media, Serum-Free; Deoxyribonucleic acid; DNA; DNA Replication - drug effects; Electrophoresis, Polyacrylamide Gel; Fundamental and applied biological sciences. Psychology; Insulin; Insulin - pharmacology; Insulin-Like Growth Factor I - pharmacology; Interleukin-3 - pharmacology; Interleukin-4 - pharmacology; Kinetics; Mast cells; Mice; Molecular and cellular biology; Peptide Mapping; Phosphatidylinositol 3-Kinases; Phosphoproteins - isolation & purification; Phosphoproteins - metabolism; Phosphorylation; Phosphotransferases - metabolism; Phosphotyrosine; Receptor, Insulin - metabolism; Receptors; Recombinant Proteins - metabolism; Recombinant Proteins - pharmacology; Signal transduction; Signal Transduction - drug effects; T lymphocytes; Thymidine - metabolism; Transfection; Tyrosine - analogs & derivatives; Tyrosine - analysis
• ISSN: 0027-8424; 1091-6490
• DOI: 10.1073/pnas.90.9.4032

Interleukin 4 (IL-4), insulin, and insulin-like growth factor I (IGF-I) efficiently induced DNA synthesis in the IL-3-dependent murine myeloid cell lines FDC-P1 and FDC-P2. Although these factors could not individually sustain long-term growth of these lines, a combination of IL-4 with either insulin or IGF-I did support continuous growth. The principal tyrosine-phosphorylated substrate observed in FDC cells stimulated with IL-4, previously designated 4PS, was of the same size (170 kDa) as the major substrate phosphorylated in response to insulin or IGF-I. These substrates had phosphopeptides of the same size when analyzed by digestion with Staphylococcus aureus V8 protease, and each tightly associated with the 85-kDa component of phosphatidylinositol 3-kinase after factor stimulation. IRS-1, the principal substrate phosphorylated in response to insulin or IGF-I stimulation in nonhematopoietic cells, is similar in size to 4PS. However, anti-IRS-1 antibodies failed to efficiently precipitate 4PS, and some phosphopeptides generated by V8 protease digestion of IRS-1 were distinct in size from the phosphopeptides of 4PS. Nevertheless, IL-4, insulin, and IGF-I were capable of stimulating tyrosine phosphorylation of IRS-1 in FDC cells that expressed this substrate as a result of transfection. These findings indicate that (i) IL-4, insulin, and IGF-I use signal transduction pathways in FDC lines that have at least one major feature in common, the rapid tyrosine phosphorylation of 4PS, and (ii) insulin and IGF-I stimulation of hematopoietic cell lines leads to the phosphorylation of a substrate that may be related to but is not identical to IRS-1.