Regulation of Master Regulators: A tale of Many IGF Binding Proteins
Cunming Duan*
Department of Molecular, Cellular and Developmental Biology, University of Michigan, Ann Arbor, MI 48109
Insulin-like Growth Factors (IGFs) are key growth-promoting signaling peptides that act as both endocrine hormones and autocrine/paracrine growth factors. In the bloodstream and in local tissues, most IGF molecules are bound by one of the members of the IGF binding protein (IGFBP) family, of which 6 distinct types exist. These proteins bind to IGF with an equal or greater affinity than the IGF1 receptor and are thus in a key position to regulate IGF signaling globally and locally. Binding to an IGFBP increases the half-life of IGF in the circulation and prevents the potential binding to the insulin receptor. In addition to these classical roles, IGFBPs have been shown to modulate IGF signaling locally under various conditions. Although members of the IGFBP family share significant sequence homology, they each have unique structural features and play distinct roles. These IGFBP genes also have different modes of regulation and distinct expression patterns. Some IGFBPs have been found to bind to their own receptors or to translocate into the interior compartments of cells where they may execute IGF-independent actions. In this talk, I will explore the emerging theme that many IGFBP functions have evolved to allow the targeted adjustment of IGF signaling under stressful or pathophysiological conditions. We propose that evolution has tended to retain an array of IGFBPs in order to facilitate fine-tuning of IGF signaling.
Key words, IGF, IGFBP, growth regulation, evolution, signal transduction
Cunming Duan*
Department of Molecular, Cellular and Developmental Biology, University of Michigan, Ann Arbor, MI 48109
Insulin-like Growth Factors (IGFs) are key growth-promoting signaling peptides that act as both endocrine hormones and autocrine/paracrine growth factors. In the bloodstream and in local tissues, most IGF molecules are bound by one of the members of the IGF binding protein (IGFBP) family, of which 6 distinct types exist. These proteins bind to IGF with an equal or greater affinity than the IGF1 receptor and are thus in a key position to regulate IGF signaling globally and locally. Binding to an IGFBP increases the half-life of IGF in the circulation and prevents the potential binding to the insulin receptor. In addition to these classical roles, IGFBPs have been shown to modulate IGF signaling locally under various conditions. Although members of the IGFBP family share significant sequence homology, they each have unique structural features and play distinct roles. These IGFBP genes also have different modes of regulation and distinct expression patterns. Some IGFBPs have been found to bind to their own receptors or to translocate into the interior compartments of cells where they may execute IGF-independent actions. In this talk, I will explore the emerging theme that many IGFBP functions have evolved to allow the targeted adjustment of IGF signaling under stressful or pathophysiological conditions. We propose that evolution has tended to retain an array of IGFBPs in order to facilitate fine-tuning of IGF signaling.
Key words, IGF, IGFBP, growth regulation, evolution, signal transduction