Role of Post Translational Modifications in Modifying the Biologic Activity of Insulin Like Growth Factor Binding Proteins

  • David R. Clemmons
Part of the Advances in Experimental Medicine and Biology book series (AEMB, volume 343)


The six insulin-like growth factor binding proteins (IGFBP’s) have been shown to be produced by a variety of cell types. When present in the local pericellular microenvironment these proteins have very high affinity for insulin like factors (IGF’s) and can regulate the amount of each IGF that is available to bind to receptors. Estimates of the affinity constants for each protein show that they are at least equal to the Type l IGF receptor and in many cases significantly greater. Studies of the biologic actions of IGF-I and II in vitro in the presence of IGFBP’s have shown that the BP’s consistently inhibit the acute metabolic effects of IGF-I such as glucose transport and lipid synthesis. However, analysis of longer term effects such as stimulation of protein synthesis and DNA synthesis have shown that binding proteins can either enhance or inhibit these IGF-I actions. The major focus of research in our laboratory has been to determine if post-translational modifications of these binding proteins result in alterations in their ability to either inhibit or stimulate IGF-I actions. Studies in our lab have linked changes in several of these post-translational modifications to changes in the cellular responsiveness to IGF-I.


Smooth Muscle Cell Culture Fibroblast Conditioned Medium Wound Breaking Strength Acute Metabolic Effect Confluent Smooth Muscle Cell 
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  1. 1.
    Jones JI. D’Ercole AJ, Camacho-Hubner C, Clemmons DR. Phosphorylation of insulin-like growth factor binding protein in cell culture and in vivo: effects on affinity for IGF-I. Proc Natl Acad Sci USA. 88:7481–7485 (1991).PubMedCrossRefGoogle Scholar
  2. 2.
    Frost JP, Tseng LT. Insulin-like growth factor binding protein-1 is phosphorylatãd by cultured human endometrial cells and multiple protein kinases in vitro. J Biol Chem. 266:18082–18088 (1991).PubMedGoogle Scholar
  3. 3.
    Jyung J, Mustoe T, Busby WH, Clemmons DR. Increased wound breaking strength induced by insulin-like growth factor-1 in combination with IGF binding protein-1. Surg. In press (1993).Google Scholar
  4. 4.
    Jones JI, Busby WH, Wright G, Smith CE, Kimack NM, Clemmons DR. Identification of the sites of phosphorylation in insulin like growth factor binding protein-1: Regulation of its affinity by phosphorylation of serine 101. J Biol Chem. 268:1125–1131 (1993).PubMedGoogle Scholar
  5. 5.
    Jones, JI, Busby, WH, Gockerman, A, Camacho-Hubner, C, Clemmons, DR. Extracellular matrix contains insulin-like growth factor for IGF binding protein 5: potentiation of the effects of IGF-I. J. Cell Biol. 121:679–687 (1993).PubMedCrossRefGoogle Scholar
  6. 6.
    McCusker RH, Camacho-Hubner C, Bayne ML, Cascieri MA, Clemmons DR. Insulin-like growth factor (IGF) binding to human fibroblast and glioblastoma cells: The modulating effect of cell released IGF binding proteins (IGFBPs). J Cell Physiol. 144:244–253 (1990).PubMedCrossRefGoogle Scholar
  7. 7.
    Cohick WS, Gockerman A, Clemmons DR. Vascular smooth muscle cells synthesize two forms of insulin like growth factor binding proteins (IGFBP) which are regulated differently by the IGF’s. J. Cell Physiol; in press (1993).Google Scholar
  8. 8.
    Camacho-Hubner C , Busby WH , McCusker RH , Wright G , Clemmons DR . Identification of the forms of -insulin-like growth factor binding proteins produced by human fibroblasts and the mechanisms that regulate their secretion. J Biol Chem. 267:11949–11956 (1992).PubMedGoogle Scholar
  9. 9.
    Andress DL, Birnbaum RS. A novel human insulin-like growth factor binding protein secreted by osteoblast cells. Biochem Biophys Res Commun. 176:213–218 (1991).PubMedCrossRefGoogle Scholar

Copyright information

© Springer Science+Business Media New York 1994

Authors and Affiliations

  • David R. Clemmons
    • 1
  1. 1.Division of Endocrinology, Department of MedicineUniversity of North CarolinaChapel HillUSA

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