Phylogenetic analysis of the insulin-like growth factor binding protein (IGFBP) and IGFBP-related protein gene families

Abstract

Insulin-like growth factor (IGF) activity is regulated by six high affinity binding proteins (IGFBPs) and possibly by some of the nine IGFBP-related proteins (IGFBP-rPs). To determine the phylogenetic relationship of this proposed gene superfamily, we conducted maximum likelihood (ML) and Bayesian inference analyses on a matrix of amino acid sequences from a diversity of vertebrate species. A single most likely phylogram, ML bootstrap, and Bayesian consensus tree of 10,000,000 generations revealed a monophyletic IGFBP lineage independent of the IGFBP-rPs. The IGFBPs segregated into three distinct clades: IGFBP-1, -3, and -6. Subsequent gene duplication events within the IGFBP-1 and -3 clades resulted in the production and divergence of IGFBP-2 and -4 within the IGFBP-1 clade and IGFBP-5 in the IGFBP-3 clade. By contrast, the IGFBP-rPs were distributed paraphyletically into two clades: IGFBP-rP1, 5, and 6 in one clade and the CCN family (IGFBPrP2-4,7-9) in another. A recently identified IGFBP-3 homolog in rainbow trout localized to the IGFBP-2 subclade. Subsequence analysis identified a RGD motif common to IGFBP-2 orthologs, but did not identify the nuclear localization sequence present in IGFBP-3 and -5 homologs. The putative trout IGFBP-3 was 36-55% identical to different IGFBP-2 proteins, but only 24-27% identical to IGFBP-3 proteins. These results suggest that the IGFBPs and IGFBP-rPs are at best distantly related and that the limited similarities likely resulted from exon shuffling. They also suggest that rainbow trout, and possibly other salmonids, possess two IGFBP-2 paralogs as the putative trout IGFBP-3 is misannotated.

Regulation of endocrine and paracrine sources of Igfs and Gh receptor during compensatory growth in hybrid striped bass (Morone chrysops×Morone saxatilis)

“…The 40 kDa Igfbp is thought to be a putative mammalian Igfbp-3 based on physiological responses and molecular weight (Siharath et al 1995a,b, Shimizu et al 2003, but according to recent phylogenic analysis may be an Igfbp-2 paralog (Rodgers et al 2008). The 40 kDa Igfbp in our study displays distinct expression patterns in relation to feed restriction and CG (Fig.…”

“…Based on molecular weight (MW) and physiological responses, including those in striped bass , Siharath et al 1995a, the 40 kDa Igfbp detected in this study is likely the mammalian equivalent of Igfbp-3, or alternatively an Igfbp-2 paralog, which is reported to increase Igf1 half-life and regulate its availability to target tissues (Kelley et al 2001, Shimizu et al 2003, Rodgers et al 2008. Levels of the 40 kDa Igfbp paralleled those of circulating Igf1, declining during catabolism and increasing to levels of control fish by termination of the CG response.…”

“…The anabolic effects of both Igf1 and Igf2 are mediated by Igf-binding proteins (Igfbps), four of which have been identified in fishes at the protein level (Igfbp-1, -2, -3, and -5; Shimizu et al 2003. The putative , which actually may be an Igfbp-2 paralog (Rodgers et al 2008), is most commonly associated with anabolic states in fishes and may facilitate Igf actions by increasing Igf half-life in the blood and by mediating their transport from the vascular space to target tissues (reviewed by Kelley et al 2006). Despite evidence supporting the role of the Gh/Igf axis in regulating growth in ectotherms generally and teleosts specifically, few studies have addressed how most components correspond to variable growth phases, including the accelerated state seen with CG.…”

Dynamic transcriptional regulation of autocrine/paracrine igfbp1, 2, 3, 4, 5, and 6 in the skeletal muscle of the fine flounder during different nutritional statuses

“…igfbp3 was misnamed, with the igfbp2 paralog 2 being the real igfbp isolated (Bower et al 2008, Rodgers et al 2008, Ocampo Dasa et al 2011. The similarity among different Igfbps and/or other related proteins has been a common problem in the correct identification of Igfbps (Rodgers et al 2008).…”

“…The similarity among different Igfbps and/or other related proteins has been a common problem in the correct identification of Igfbps (Rodgers et al 2008). All Igfbps have a common structure with a highly conserved N-terminal (also known as IGFBP domain), a conserved C-terminal domain (also known as thyroglobulin type-1 domain), and an internal variable L-domain (Duan & Xu 2005).…”