Specifying the cellular responses to IGF signals: roles of IGF-binding proteins

Abstract

Regulation of peptide growth factor/hormone activities by secreted hormone-binding proteins has emerged as a common theme in cell-cell signaling. Among the beststudied examples are members of the IGF-binding protein (IGFBP) gene family. These secreted proteins bind the IGF ligands with equal or even greater affinities than do the IGF receptors, and therefore are placed in a critical regulatory position between IGFs and their cell surface receptors. The circulating IGF/IGFBP complexes prolong the half-lives of IGFs and buffer the potential hypoglycemic effects of IGFs. Locally expressed IGFBPs provide a means of localizing IGFs in specific cells and can alter the IGF biological activity. While some members of the IGFBP gene family have been consistently shown to inhibit IGF actions by preventing them from gaining access to the IGF receptors, others potentiate IGF actions by facilitating the ligand-receptor interaction. Furthermore, recent studies indicate that some IGFBPs can regulate several cellular processes through ligandindependent mechanisms. This review will focus on the roles of IGFBPs in vascular smooth muscle cells. A conceptual model of the molecular mechanisms by which IGFBPs act to determine the specific physiological outcomes of IGF stimulation is proposed and discussed.

Identification of Selective Basophil Chemoattractants in Human Nasal Polyps as Insulin-Like Growth Factor-1 and Insulin-Like Growth Factor-2

“…Fibroblasts are a significant source of IGFs, as well as being responsive to these growth factors in terms of proliferation and collagen production (41). IGF-1 is a growth and differentiation factor for myocytes and can also stimulate proliferation and chemotaxis of vascular and airway smooth muscle cells (42). IGF-1R is expressed by T cells (43)(44)(45) and other leukocytes, and IGF-1 has been shown to promote T cell proliferation and chemotaxis (43).…”

Insulin-like Growth Factor Binding Protein-4 Differentially Inhibits Growth Factor-induced Angiogenesis

“…IGFBPs are known to regulate IGF signaling by binding to IGF-1, thereby modulating the ability of this growth factor to bind and activate its cognate receptors (19,20). Although certain members of the IGFBP family may have both stimulatory and inhibitory activity, IGFBP-4 has been predominately associated with inhibitory activity by reducing IGF-1R signaling (19,20,35,36).…”

“…Interestingly, members of the insulin-like growth factor binding protein (IGFBP) family are rapidly gaining attention as critical regulators of a variety of normal physiological and pathological processes, because IGFBPs have been shown to regulate diverse cellular events such as proliferation, migration, apoptosis, and differentiation, all crucial processes thought to govern specific steps within the angiogenic cascade (19,20). IGFBPs are an important family of secreted proteins that exhibit high affinity binding to the peptide growth factors IGF-1 and IGF-2, thereby functioning to modulate their bioavailability and binding to IGF receptors (19,20).…”

“…IGFBPs are an important family of secreted proteins that exhibit high affinity binding to the peptide growth factors IGF-1 and IGF-2, thereby functioning to modulate their bioavailability and binding to IGF receptors (19,20).…”

αCAR IGF‐1 vector targeting of motor neurons ameliorates disease progression in ALS mice

“…The IGF‐1 family of growth factors (somatomedins) includes three structurally related ligands ( IGF‐1 , IGF‐2 and insulin), their respective receptors, and at least six IGF‐1 binding proteins ( IGFBP ) 5. They are produced in multiple cells and exert different physiological roles by binding to distinct tyrosine kinase receptors and activating multiple downstream signaling cascades 6.…”