Two Types of Receptor for Insulin-Like Growth Factors are Expressed on Normal and Malignant Cells from Mammalian Brain

  • Steen Gammeltoft
  • Robert Ballotti
  • Finn Cilius Nielsen
  • Aline Kowalski
  • Emmanuel Van Obberghen


Insulin-like growth factors (IGFs) I and II stimulate cell growth in several mammalian tissues. The cellular actions are mediated by interactions with two types of IGF receptor, which have been characterized by their protein structure, binding specificity, and intrinsic tyrosine kinase activity. Recently, expression of IGF I and IGF II genes and production of IGFs have been demonstrated in mammalian brain. In search for the function of IGF I and IGF II in the central nervous system, we have looked for the presence of IGF receptors on normal and malignant cells from fetal and adult mammalian brain and the growth-promoting effects of IGFs on primary cultures of fetal rat astrocytes.

We have shown that two types of IGF receptor are present on plasma membranes from adult rat brain, on fetal rat astrocytes and on human glioma cells. Type I IGF receptor is composed of 2 types of subunits: α-subunits which binds IGF I and IGF II with high affinity and insulin weakly, and β-subunits which show tyrosine kinase activity and autophosphorylation stimulated by IGF I and IGF II with almost similar potency. The molecular size of the type I IGF receptor α-subunit is larger in cultured fetal rat astrocytes and human glioma cells than in normal adult brain (Mr ~ 130 000 Versus 115 000), whereas the β-subunit has the same electrophoretic mobility (Mr ~ 94 000). The type II IGF receptor is a monomeric protein (Mr ~ 250 000), which binds IGF II 5 times better than IGF I, and does not recognize insulin. The amounts of type II IGF rceptor are significantly higher in fetal and malignant cells than in adult brain. Based on these findings we suggest that IGF receptors in brain undergo developmental changes, which may have functional implications.

The presence of two types of IGF receptor on brain cells strongly suggests regulatory functions of IGFs in mammalian brain. Results in different laboratories including our own have shown that IGFs stimulate growth of cultured fetal rat astrocytes indicating a role of IGF I and IGF II as growth promotors in the central nervous system. It seems possible that the growth effect is mediated by activation of the type I IGF receptor tyrosine kinase.


Insulin Receptor Mammalian Brain Human Glioma Cell Intrinsic Tyrosine Kinase Activity Retinal Capillary Endothelial Cell 
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Copyright information

© Plenum Press, New York 1987

Authors and Affiliations

  • Steen Gammeltoft
    • 1
  • Robert Ballotti
    • 2
  • Finn Cilius Nielsen
    • 1
  • Aline Kowalski
    • 2
  • Emmanuel Van Obberghen
    • 2
  1. 1.Department of Clinical ChemistryBispebjerg HospitalCopenhagenDenmark
  2. 2.INSERM U 145, Faculté de MédicineUniversité de NiceNiceFrance

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