Abstract
Like many other cytokines and growth factors, interleukin-6 (IL-6) activates p21ras. However, the precise biochemical mechanisms inducing this activation are unknown. Therefore, we investigated the effects of IL-6 on some recently identified signaling intermediates, Shc (Src homology and collagen) and Grb2 (growth factor receptor bound protein 2), known to activate p21ras. In the multiple myeloma cell line LP-1, IL-6 stimulated the tyrosine phosphorylation of Shc in a time- and concentration-dependent manner. This led to the complex formulation of Shc with Grb2, an adaptor protein known to relocate a p21ras-GDP exchange factor. Sos1 (Son-of-sevenless), to the cell membrane. Taken together, these findings suggest that IL-6 might activate the Ras signaling pathway via tyrosine phosphorylation of Shc and subsequent recruitment of Grb2. Further studies will elucidate which of the IL-6 receptor associated non-receptor tyrosine kinases of the Src kinase or Janus kinase family, mediate these effects.
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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Adaptor Proteins, Vesicular Transport*
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Enzyme Induction / immunology
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ErbB Receptors / metabolism*
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Female
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GRB2 Adaptor Protein
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Humans
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Interleukin-6 / pharmacology*
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Kinetics
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Macromolecular Substances
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Middle Aged
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Multiple Myeloma / enzymology
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Multiple Myeloma / immunology*
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Multiple Myeloma / metabolism*
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Phosphorylation / drug effects
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Protein-Tyrosine Kinases / metabolism*
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Proteins / drug effects
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Proteins / metabolism*
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Proto-Oncogene Proteins p21(ras) / biosynthesis
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Receptor, ErbB-2 / metabolism*
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Shc Signaling Adaptor Proteins
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Signal Transduction / immunology*
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Src Homology 2 Domain-Containing, Transforming Protein 1
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Tumor Cells, Cultured
Substances
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Adaptor Proteins, Signal Transducing
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Adaptor Proteins, Vesicular Transport
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GRB2 Adaptor Protein
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GRB2 protein, human
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Interleukin-6
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Macromolecular Substances
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Proteins
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SHC1 protein, human
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Shc Signaling Adaptor Proteins
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Src Homology 2 Domain-Containing, Transforming Protein 1
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epidermal growth factor receptor-neu receptor
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ErbB Receptors
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Protein-Tyrosine Kinases
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Receptor, ErbB-2
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HRAS protein, human
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Proto-Oncogene Proteins p21(ras)