Reciprocal Modulation of Binding of Lysosomal Enzymes and Insulin-Like Growth Factor-II (IGF-II) to the Mannose 6- Phosphate/IGF-II Receptor

  • Peter Nissley
  • Wieland Kiess
Part of the Advances in Experimental Medicine and Biology book series (AEMB, volume 293)


The discovery by Morgan et al.1 that the human IGF-II receptor is 80% homologous to the bovine cation-independent mannose 6-phosphate (Man-6-P) receptor led them to propose that the receptor is bifunctional, binding both a large number of lysosomal enzymes through the Man-6-P recognition site, and the growth factor, IGF-II. Later, Komfeld’s and Czech’s laboratories reported that the avian and amphibian Man-6-P receptors did not bind IGF-II, suggesting that the bifunctional property of the receptor may be confined to mammals.2,3 Did the mammalian receptor gene simply pick up a nucleotide sequence encoding an IGF-II binding site, enabling the receptor to provide a degradative pathway for IGF-II, or are there important interactions of the two disparate classes of ligands for binding to the receptor? These interactions could result in reciprocal modulation of the targeting of lysosomal enzymes by IGF-II, on the one hand, and the modulation of IGF-II degradation and IGF-II stimulated biologic responses by lysosomal enzymes, on the other. We will briefly summarize our experimental results which provide evidence for reciprocal inhibition of binding of the two classes of ligands for the mammalian Man-6-P/ IGF-II receptor.


Cellular Uptake Lysosomal Enzyme Reciprocal Modulation High Extracellular Concentration Disuccinimidyl Suberate 


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Copyright information

© Plenum Press, New York 1991

Authors and Affiliations

  • Peter Nissley
    • 1
  • Wieland Kiess
    • 2
  1. 1.Metabolism Branch, National Cancer InstituteNational Institutes of HealthBethesdaUSA
  2. 2.Children’s HospitalUniversity of MunichMunichGermany

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