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Insulin-like growth factor-binding protein 5 (IGFBP-5) interacts with a four and a half LIM protein 2 (FHL2).

Abstract
Recent studies using insulin-like growth factor I (IGF-I) knockout mice demonstrate that IGF-binding protein (IGFBP)-5, an important bone formation regulator, itself is a growth factor with cellular effects not dependent on IGFs. Because IGFBP-5 contains a nuclear localization sequence that mediates transport of IGFBP-5 into the nucleus, we propose that IGFBP-5 interacts with nuclear proteins to affect transcription of genes involved in bone formation. We therefore undertook studies to identify proteins that bind to IGFBP-5 using IGFBP-5 as bait in a yeast two-hybrid screen of a U2 human osteosarcoma cDNA library. Five related clones that interacted strongly with the bait corresponded to the FHL2 gene, which contains four and a half LIM domains. Co-immunoprecipitation studies with lysates from U2 cells overexpressing FHL2 and IGFBP-5 confirmed that interaction between IGFBP-5 and FHL2 occurs in whole cells. In vitro interaction studies revealed that purified FHL2 interacted with IGFBP-5 but not with IGFBP-3, -4, or -6. Northern blot analysis showed that FHL2 was strongly expressed in human osteoblasts. Nuclear localization of both FHL2 and IGFBP-5 was evident from Western immunoblot analysis and immunofluorescence. The role of FHL2 as an intracellular mediator of the effects of IGFBP-5 and other osteoregulatory agents in osteoblasts will need to be verified in future studies.
AuthorsYousef G Amaar, Garrett R Thompson, Thomas A Linkhart, Shin-Tai Chen, David J Baylink, Subburaman Mohan
JournalThe Journal of biological chemistry (J Biol Chem) Vol. 277 Issue 14 Pg. 12053-60 (Apr 05 2002) ISSN: 0021-9258 [Print] United States
PMID11821401 (Publication Type: Journal Article, Research Support, Non-U.S. Gov't, Research Support, U.S. Gov't, Non-P.H.S., Research Support, U.S. Gov't, P.H.S.)
Chemical References
  • DNA, Complementary
  • FHL2 protein, human
  • Fhl2 protein, mouse
  • Homeodomain Proteins
  • Insulin-Like Growth Factor Binding Protein 3
  • Insulin-Like Growth Factor Binding Protein 4
  • Insulin-Like Growth Factor Binding Protein 5
  • Insulin-Like Growth Factor Binding Protein 6
  • LIM-Homeodomain Proteins
  • Muscle Proteins
  • Recombinant Proteins
  • Transcription Factors
Topics
  • Active Transport, Cell Nucleus
  • Animals
  • Blotting, Northern
  • Blotting, Western
  • Cell Nucleus (metabolism)
  • Cytoplasm (metabolism)
  • DNA, Complementary (metabolism)
  • Gene Library
  • Genetic Vectors
  • Homeodomain Proteins (chemistry, metabolism)
  • Humans
  • Insulin-Like Growth Factor Binding Protein 3 (metabolism)
  • Insulin-Like Growth Factor Binding Protein 4 (metabolism)
  • Insulin-Like Growth Factor Binding Protein 5 (chemistry, metabolism)
  • Insulin-Like Growth Factor Binding Protein 6 (metabolism)
  • LIM-Homeodomain Proteins
  • Mice
  • Microscopy, Fluorescence
  • Muscle Proteins
  • Plasmids (metabolism)
  • Precipitin Tests
  • Protein Binding
  • Protein Structure, Tertiary
  • Recombinant Proteins (metabolism)
  • Retroviridae (genetics)
  • Transcription Factors
  • Transfection
  • Tumor Cells, Cultured
  • Two-Hybrid System Techniques

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