Limited redundancy of survival signals from the type 1 insulin-like growth factor receptor

Endocrinology. 2001 Mar;142(3):1073-81. doi: 10.1210/endo.142.3.7991.

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

  • Research Support, U.S. Gov't, P.H.S.

MeSH terms

  • Adaptor Proteins, Signal Transducing*
  • Adaptor Proteins, Vesicular Transport*
  • Animals
  • Apoptosis / drug effects
  • Cell Line
  • Cell Survival / physiology
  • Chromones / pharmacology
  • Enzyme Activation / physiology
  • Enzyme Inhibitors / pharmacology
  • Flavonoids / pharmacology
  • Hematopoietic Stem Cells / physiology*
  • Insulin Receptor Substrate Proteins
  • Mice
  • Mitogen-Activated Protein Kinases / metabolism
  • Morpholines / pharmacology
  • Phosphoproteins / metabolism
  • Phosphorylation
  • Protein-Serine-Threonine Kinases*
  • Proteins / metabolism
  • Proto-Oncogene Proteins / metabolism
  • Proto-Oncogene Proteins c-akt
  • Proto-Oncogene Proteins c-raf / pharmacology
  • Receptor, IGF Type 1 / physiology*
  • Shc Signaling Adaptor Proteins
  • Signal Transduction / drug effects
  • Signal Transduction / physiology*
  • Src Homology 2 Domain-Containing, Transforming Protein 1

Substances

  • Adaptor Proteins, Signal Transducing
  • Adaptor Proteins, Vesicular Transport
  • Chromones
  • Enzyme Inhibitors
  • Flavonoids
  • Insulin Receptor Substrate Proteins
  • Irs1 protein, mouse
  • Morpholines
  • Phosphoproteins
  • Proteins
  • Proto-Oncogene Proteins
  • Shc Signaling Adaptor Proteins
  • Shc1 protein, mouse
  • Src Homology 2 Domain-Containing, Transforming Protein 1
  • 2-(4-morpholinyl)-8-phenyl-4H-1-benzopyran-4-one
  • Receptor, IGF Type 1
  • Protein-Serine-Threonine Kinases
  • Proto-Oncogene Proteins c-akt
  • Proto-Oncogene Proteins c-raf
  • Mitogen-Activated Protein Kinases
  • 2-(2-amino-3-methoxyphenyl)-4H-1-benzopyran-4-one