IGF-binding protein-5: flexible player in the IGF system and effector on its own.
The multiple activities of IGF-I and -II are modulated by a family of IGF-binding proteins (IGFBP-1 to -6). Although structurally related, each IGFBP has unique properties and exerts specific functions. IGFBP-5 is the most conserved IGFBP across species and was identified as an essential regulator of physiological processes in bone, kidney and mammary gland. In addition, IGFBP-5 appears to play a decisive role in the control of proliferation of specific tumour cell types. In many situations IGFBP5 exerts biological activities in the absence of IGFs, indicating the existence of IGF-independent actions. This concept was supported by the unexpected localisation of IGFBP-5 in the nucleus and the description of IGFBP-5-specific membrane-bound IGFBP-5 receptor(s). The scope of this review is to summarise the available information about the structure of IGFBP-5 and the regulation of its expression. Furthermore, the potential significance of IGFBP-5 in the regulation of physiological processes will be critically analysed in the light of recent experimental data.
Schneider
M R
MR
Institute of Molecular Animal Breeding, Gene Centre of the University of Munich, Feodor-Lynen-Strasse 25, D-81377 Munich, Germany. ms2278@columbia.edu
Wolf
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Hoeflich
A
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Lahm
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D000818:Animals; D001842:Bone and Bones / Q000378:metabolism; D002467:Cell Nucleus / Q000378:metabolism; D005109:Extracellular Matrix / Q000378:metabolism; D005260:Female; D005786:Gene Expression Regulation; D006801:Humans; D018975:Insulin-Like Growth Factor Binding Protein 5 / Q000235:genetics / Q000502:physiology*; D007334:Insulin-Like Growth Factor I / Q000378:metabolism*; D007335:Insulin-Like Growth Factor II / Q000378:metabolism*; D007668:Kidney / Q000378:metabolism; D008297:Male; D008321:Mammary Glands, Animal / Q000378:metabolism; D008565:Membrane Proteins / Q000378:metabolism; D009132:Muscles / Q000378:metabolism; D009369:Neoplasms / Q000378:metabolism; D010053:Ovary / Q000378:metabolism; D011485:Protein Binding; D017434:Protein Structure, Tertiary
D018975:Insulin-Like Growth Factor Binding Protein 5; D008565:Membrane Proteins; D007334:Insulin-Like Growth Factor I; D007335:Insulin-Like Growth Factor II