The insulin-like growth factor binding protein superfamily: new perspectives.
The insulin-like growth factor (IGF) binding proteins (IGFBPs) were initially identified as carrier proteins for IGF-I and IGF-II in a variety of biologic fluids. Their presumed function was to protect IGF peptides from degradation and clearance, increase the half-life of the IGFs, and deliver them to appropriate tissue receptors. The concept of IGFBPs as simple carrier proteins has been complicated, however, by a number of observations: 1) the six IGFBPs vary in their tissue expression and their regulation by other hormones and growth factors; 2) the IGFBPs are subjected to proteolytic degradation, thereby altering their affinities for the IGFs; 3) IGFBP-3 and IGFBP-5, in addition to binding IGFs, also can associate with an acid-labile subunit, thereby increasing further the half-life of the IGFs; 4) in addition to modifying the access of IGF peptides to IGF and insulin receptors, several of the IGFBPs may be capable of increasing IGF action; 5) some of the IGFBPs may be capable of IGF-independent regulation of cell growth; 6) some of the IGFBPs are associated with cell membranes or possibly with membrane receptors; and 7) some of the IGFBPs have nuclear recognition sites and may be found within the nucleus. Additionally, a number of cDNAs identified recently have been found to encode proteins that bind IGFs, but with substantially lower affinities than is the case with IGFBPs. The N-terminal regions of the predicted proteins are structurally homologous to the classic IGFBPs, with conservation of the cysteine-rich region. These observations suggest that these low-affinity binders are members of an IGFBP superfamily, capable of regulating cell growth by both IGF-dependent and IGF-independent mechanisms.insulin-like growth factor, insulin-like growth factor binding proteins.
Rosenfeld
R G
RG
Department of Pediatrics, Oregon Health Science University, Portland, Oregon 97201, USA. rosenfer@ohsu.edu
Hwa
V
V
Wilson
L
L
Lopez-Bermejo
A
A
Buckway
C
C
Burren
C
C
Choi
W K
WK
Devi
G
G
Ingermann
A
A
Graham
D
D
Minniti
G
G
Spagnoli
A
A
Oh
Y
Y
D006801:Humans; D018969:Insulin-Like Growth Factor Binding Proteins / Q000145:classification / Q000502:physiology; D008970:Molecular Weight
D018969:Insulin-Like Growth Factor Binding Proteins