Document Detail


Role of insulin-like growth factor binding proteins in the control of IGF actions.
MedLine Citation:
PMID:  8817679     Owner:  NLM     Status:  MEDLINE    
Abstract/OtherAbstract:
The insulin-like growth factor binding proteins have been shown to modify IGF actions. IGFBP-5 binds to extracellular matrix (ECM) and its ability to potentiate IGF activity is dependent upon the amount that is ECM associated. To determine the specific regions of IGFBP-5 that are required for ECM association, site directed mutagenesis has been used to prepare several forms of IGFBP-5. Mutants that have had the amino acids between positions 201 and 218 altered have been useful. Mutation of the lysine 211 resulted in no change in the affinity of IGFBP-5 for ECM or heparin Sepharose; however, it resulted in a major reduction in affinity for IGF-I following heparin binding. Other mutations which disrupted heparin binding also resulted in loss of this affinity shift. Most distruptive were mutations of amino acids 211, 214, 217 and 218 and 202, 206 and 207. Mutation of residues 201 plus 202 had some effect, but substitution for 207, 211, 217 and 218 had no effect. When binding to intact ECM was analyzed, similar results were obtained. This suggests that amino acids 202, 206 and 214 are definitely involved in heparin and ECM binding. When binding to proteoglycans such as tenascin and heparin sulfate proteoglycan was analyzed, similar results were obtained. IGFBP-5 also binds to other proteins in ECM, including type IV collagen and plasminogen activator inhibitor-I. Specific antisera for plasminogen activator inhibitor-1 can coprecipitate IGFBP-5. IGFBPs are degraded by specific proteases. Three proteases that degrade IGFBP-2, -4 and -5 have been characterized. They are serine proteases that cleave these proteins at basic residues. Although several well characterized serine proteases cleave IGFBP-4 or -5, the proteases in cell conditioned media appear to be distinct.
Authors:
D R Clemmons; W H Busby; T Arai; T J Nam; J B Clarke; J I Jones; D K Ankrapp
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Publication Detail:
Type:  Journal Article; Research Support, U.S. Gov't, P.H.S.; Review    
Journal Detail:
Title:  Progress in growth factor research     Volume:  6     ISSN:  0955-2235     ISO Abbreviation:  Prog. Growth Factor Res.     Publication Date:  1995  
Date Detail:
Created Date:  1996-12-05     Completed Date:  1996-12-05     Revised Date:  2007-11-14    
Medline Journal Info:
Nlm Unique ID:  8912757     Medline TA:  Prog Growth Factor Res     Country:  ENGLAND    
Other Details:
Languages:  eng     Pagination:  357-66     Citation Subset:  IM    
Affiliation:
Department of Medicine, University of North Carolina, School of Medicine, Chapel Hill 27599, USA.
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MeSH Terms
Descriptor/Qualifier:
Animals
Extracellular Matrix / metabolism
Insulin-Like Growth Factor Binding Protein 1 / metabolism
Insulin-Like Growth Factor Binding Protein 3 / metabolism
Insulin-Like Growth Factor Binding Protein 4 / metabolism
Insulin-Like Growth Factor Binding Protein 5 / metabolism
Insulin-Like Growth Factor Binding Proteins / physiology*
Phosphorylation
Proteoglycans / metabolism
Somatomedins / physiology*
Grant Support
ID/Acronym/Agency:
AGO2331/AG/NIA NIH HHS; HL26309/HL/NHLBI NIH HHS
Chemical
Reg. No./Substance:
0/Insulin-Like Growth Factor Binding Protein 1; 0/Insulin-Like Growth Factor Binding Protein 3; 0/Insulin-Like Growth Factor Binding Protein 4; 0/Insulin-Like Growth Factor Binding Protein 5; 0/Insulin-Like Growth Factor Binding Proteins; 0/Proteoglycans; 0/Somatomedins

From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine


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