title: IGF-binding protein-4: biochemical characteristics and functional consequences.
abstract: IGFs have multiple functions regarding cellular growth, survival and differentiation under different physiological and pathological conditions. IGF effects are modulated systemically and locally by six high-affinity IGF-binding proteins (IGFBP-1 to -6). Despite their structural similarity, each IGFBP has unique properties and exhibits specific functions. IGFBP-4, the smallest IGFBP, exists in both non-glycosylated and N-glycosylated forms in all biological fluids. It is expressed by a wide range of cell types and tIssues, and its expression is regulated by different mechanisms in a cell type-specific manner. IGFBP-4 binds IGF-I and IGF-II with similar affinities and inhibits their actions under almost all in vitro and in vivo conditions. In this review, we summarize the available data regarding the following aspects of IGFBP-4: genomic organization, protein structure-function relationship, expression and its regulation, as well as IGF-dependent and -independent actions. The biological significance of IGFBP-4 for reproductive physiology, bone formation, renal pathophysiology and cancer is discussed.
authors.affiliation: Institute of Molecular Animal Breeding and Biotechnology, Gene Center of the University of Munich, 81377 Munich, Germany. zhou@lmb.uni-muenchen.de
authors.forename: R
authors.initials: R
authors.lastname: Zhou
authors.forename: D
authors.initials: D
authors.lastname: Diehl
authors.forename: A
authors.initials: A
authors.lastname: Hoeflich
authors.forename: H
authors.initials: H
authors.lastname: Lahm
authors.forename: E
authors.initials: E
authors.lastname: Wolf
mesh_terms: D000818:Animals; D001483:Base Sequence; D002462:Cell Membrane / Q000378:metabolism; D005109:Extracellular Matrix / Q000378:metabolism; D005260:Female; D006801:Humans; D018974:Insulin-Like Growth Factor Binding Protein 4 / Q000235:genetics / Q000378:metabolism*; D007668:Kidney / Q000378:metabolism; D007674:Kidney Diseases / Q000378:metabolism; D008297:Male; D051379:Mice; D008969:Molecular Sequence Data; D009369:Neoplasms / Q000378:metabolism; D010012:Osteogenesis / Q000502:physiology; D010053:Ovary / Q000378:metabolism; D011247:Pregnancy; D011485:Protein Binding; D051381:Rats; D016415:Sequence Alignment; D013002:Somatomedins / Q000378:metabolism*; D013329:Structure-Activity Relationship; D014018:Tissue Distribution
chemical_list: D018974:Insulin-Like Growth Factor Binding Protein 4; D013002:Somatomedins