IGF-binding protein-4: biochemical characteristics and functional consequences.
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.
Zhou
R
R
Institute of Molecular Animal Breeding and Biotechnology, Gene Center of the University of Munich, 81377 Munich, Germany. zhou@lmb.uni-muenchen.de
Diehl
D
D
Hoeflich
A
A
Lahm
H
H
Wolf
E
E
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
D018974:Insulin-Like Growth Factor Binding Protein 4; D013002:Somatomedins