Abstract
The type 1 insulin-like growth factor receptor (IGF-IR) is effective in protecting cells from a variety of apoptotic injuries. In 32D murine hemopoietic cells, the IGF-IR sends three separate survival signals, through insulin receptor substrate-1, Shc, and mitochondrial Raf translocation. We report here that these three pathways for survival have a limited redundancy. If one of these pathways is blocked, the IGF-IR can still protect 32D cells from apoptosis induced by interleukin-3 withdrawal. However, when two of the three pathways are inactivated, the receptor is no longer capable to protect cells from apoptosis. The survival signal can use any two pathway combinations.
Publication types
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Research Support, U.S. Gov't, P.H.S.
MeSH terms
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Adaptor Proteins, Signal Transducing*
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Adaptor Proteins, Vesicular Transport*
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Animals
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Apoptosis / drug effects
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Cell Line
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Cell Survival / physiology
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Chromones / pharmacology
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Enzyme Activation / physiology
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Enzyme Inhibitors / pharmacology
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Flavonoids / pharmacology
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Hematopoietic Stem Cells / physiology*
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Insulin Receptor Substrate Proteins
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Mice
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Mitogen-Activated Protein Kinases / metabolism
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Morpholines / pharmacology
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Phosphoproteins / metabolism
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Phosphorylation
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Protein Serine-Threonine Kinases*
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Proteins / metabolism
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Proto-Oncogene Proteins / metabolism
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Proto-Oncogene Proteins c-akt
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Proto-Oncogene Proteins c-raf / pharmacology
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Receptor, IGF Type 1 / physiology*
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Shc Signaling Adaptor Proteins
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Signal Transduction / drug effects
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Signal Transduction / physiology*
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Src Homology 2 Domain-Containing, Transforming Protein 1
Substances
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Adaptor Proteins, Signal Transducing
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Adaptor Proteins, Vesicular Transport
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Chromones
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Enzyme Inhibitors
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Flavonoids
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Insulin Receptor Substrate Proteins
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Irs1 protein, mouse
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Morpholines
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Phosphoproteins
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Proteins
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Proto-Oncogene Proteins
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Shc Signaling Adaptor Proteins
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Shc1 protein, mouse
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Src Homology 2 Domain-Containing, Transforming Protein 1
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2-(4-morpholinyl)-8-phenyl-4H-1-benzopyran-4-one
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Receptor, IGF Type 1
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Protein Serine-Threonine Kinases
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Proto-Oncogene Proteins c-akt
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Proto-Oncogene Proteins c-raf
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Mitogen-Activated Protein Kinases
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2-(2-amino-3-methoxyphenyl)-4H-1-benzopyran-4-one