Insulin Like Growth Factor 1 Receptor Signal Transduction to the Nucleus

  • Steven A. Rosenzweig
  • Barry S. Oemar
  • Norman M. Law
  • Uma T. Shankavaram
  • Bradley S. Miller
Part of the Advances in Experimental Medicine and Biology book series (AEMB, volume 343)

Abstract

The IGF-1 receptor (IGF-1R) is a member of the tyrosine kinase class of cell surface receptors which become autophosphorylated on tyrosyl residues upon ligand binding (Czech, 1989). It has striking homology to the insulin receptor; however, each receptor maintains a unique specificity for its own ligand (Schumacher et al., 1991). The mechanism by which the binding of IGF-1 to its receptor elicits a cellular effect has been the subject of considerable research with a singular cohesive model having yet to be defined. The autophosphorylation of the IGF-1R via subunit transphosphorylation is clearly a necessary requisite for transmission of an intracellular signal, as found for the insulin receptor (Sweet et al., 1987; Ullrich and Schlessinger, 1990). In the case of other growth factor receptors with tyrosine kinase domains such as the EGF and PDGF receptors, receptor activation results in phospholipase C activation leading to 1,2-diacylglycerol and inositol 1,4,5-trisphosphate production and a corresponding increase in protein kinase C (pkC) and calcium mobilization, respectively (Berridge, 1993). Recently, evidence for a direct association between the EGF and PDGF receptors and a number of key substrates such as phospholipase C-γ, PI-3 kinase and GAP (p21ras GTPase activating protein, Cantley et al., 1991) has been demonstrated. This direct link has also been established for the IGF-1R and PI-3 kinase interactions (Cantley et al., 1991; Yamamoto et al., 1992; Lavan et al., 1992). It was recently reported that in cells stimulated with insulin in the presence of the protein tyrosine phosphatase inhibitor, phenylarsine oxide, 5–10% of the cellular GAP associates with the insulin receptor (Pronk et al., 1992).

Keywords

Tyrosine Electrophoresis Leucine Thrombin Stein 

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Copyright information

© Springer Science+Business Media New York 1994

Authors and Affiliations

  • Steven A. Rosenzweig
    • 1
  • Barry S. Oemar
    • 2
  • Norman M. Law
    • 3
  • Uma T. Shankavaram
    • 1
  • Bradley S. Miller
    • 1
  1. 1.Department of Cell and Molecular Pharmacology and Experimental TherapeuticsMedical University of South CarolinaCharlestonUSA
  2. 2.Department of Research Kantonsspital BaselUniversity of BaselBaselSwitzerland
  3. 3.Oncology and Virology Research Department, Pharmaceuticals DivisionCIBA-GEIGY, Ltd.BaselSwitzerland

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