Receptor binding, endocytosis, and mitogenesis of insulin-like growth factors I and II in fetal rat brain neurons.

Published

Journal Article

Cell surface binding, internalization, and biological effects of insulin-like growth factors (IGFs) I and II have been studied in primary neuronal cultures from developing rat brain (embryonic day 15). Two types of IGF binding sites are present on the cell surface. The IGF-I receptor alpha-subunit (Mr 125,000) binds IGF-I with a KD of 1 nM and IGF-II with 10 times lower affinity. The mannose-6-phosphate (Man-6-P)/IGF-II receptor (Mr 250,000) binds IGF-II with a KD of 0.5 nM and IGF-I with 100 times lower affinity. Surface-bound IGF-I and IGF-II are internalized by their respective receptors binding and internalization of IGF-II but not those of IGF-I. Neuronal synthesis of RNA and DNA is increased twofold by IGF-I with 10 times higher potency than IGF-II. Antibody 3637, which blocks receptor binding of IGF-II, has no effect on the DNA response to IGF-I or IGF-II. Double immunocytochemical staining with antibodies to bromodeoxyuridine and neurofilament shows that greater than 80% of the bromodeoxyuridine-positive cells become neurofilament positive. It is concluded that IGF-I and IGF-II bind to two receptors on the surface of neuronal precursor cells that mediate endocytosis and degradation of IGF-I and IGF-II. Proliferation of neuronal precursor cells is stimulated by IGF-I and IGF-II via activation of the IGF-I receptor.

Full Text

Duke Authors

Cited Authors

  • Nielsen, FC; Wang, E; Gammeltoft, S

Published Date

  • January 1, 1991

Published In

Volume / Issue

  • 56 / 1

Start / End Page

  • 12 - 21

PubMed ID

  • 1702828

Pubmed Central ID

  • 1702828

International Standard Serial Number (ISSN)

  • 0022-3042

Digital Object Identifier (DOI)

  • 10.1111/j.1471-4159.1991.tb02556.x

Language

  • eng

Conference Location

  • England