Genomes and Genes
Gene Symbol: Igfbp4
Description: insulin-like growth factor binding protein 4
Alias: AI875747, Deb2, IBP-4, IGFBP-4, insulin-like growth factor-binding protein 4, Band 3A, IGF-binding protein 4, differentially expressed in B16F10 2
- Durai R, Yang S, Sales K, Seifalian A, Goldspink G, Winslet M. Increased apoptosis and decreased proliferation of colorectal cancer cells using insulin-like growth factor binding protein-4 gene delivered locally by gene transfer. Colorectal Dis. 2007;9:625-31 pubmed..05 vs control). IGFBP-4 gene transfer increased apoptosis and decreased mitosis, but tumour volume was not significantly altered possibly due to cellular debris filling the centre of tumours. ..
- Ning Y, Hoang B, Schuller A, Cominski T, Hsu M, Wood T, et al. Delayed mammary gland involution in mice with mutation of the insulin-like growth factor binding protein 5 gene. Endocrinology. 2007;148:2138-47 pubmed..These results demonstrate that IGFBP-5, although not essential for normal growth, is required for normal mammary gland involution and can regulate mammary gland morphogenesis in response to hormone stimulation. ..
- Adashi E, Resnick C, Payne D, Rosenfeld R, Matsumoto T, Hunter M, et al. The mouse intraovarian insulin-like growth factor I system: departures from the rat paradigm. Endocrinology. 1997;138:3881-90 pubmed..Studies employing the mouse model must take into account these important distinctions relative to the more established rat paradigm. ..
- Caton J, Bringas P, Zeichner David M. IGFs increase enamel formation by inducing expression of enamel mineralizing specific genes. Arch Oral Biol. 2005;50:123-9 pubmed..These results suggest that IGFs increase enamel formation by the induction of gene expression of enamel related genes. Studies are underway to determine a possible mechanism for these factors. ..
- van Kleffens M, Groffen C, Dits N, Lindenbergh Kortleve D, Schuller A, Bradshaw S, et al. Generation of antisera to mouse insulin-like growth factor binding proteins (IGFBP)-1 to -6: comparison of IGFBP protein and messenger ribonucleic acid localization in the mouse embryo. Endocrinology. 1999;140:5944-52 pubmed..The overlapping mRNA and protein localization for IGFBP-2 and -4, on the other hand, may indicate that these IGFBPs also function in an auto- or paracrine manner. ..
- Schuller A, van Neck J, Beukenholdt R, Zwarthoff E, Drop S. IGF, type I IGF receptor and IGF-binding protein mRNA expression in the developing mouse lung. J Mol Endocrinol. 1995;14:349-55 pubmed..A possible role for IGFBPs-2, -4 and -5 is to participate in the regulation of cell-specific IGF responses during mouse lung development. ..
- Gealekman O, Gurav K, Chouinard M, Straubhaar J, Thompson M, Malkani S, et al. Control of adipose tissue expandability in response to high fat diet by the insulin-like growth factor-binding protein-4. J Biol Chem. 2014;289:18327-38 pubmed publisher..only four positively correlating (Fads3, Tmsb10, Depdc6, and Rasl12) and four negatively correlating (Asph, IGFbp4, Ppm1b, and Adcyap1r1) genes...
- Schneider M, Lahm H, Wu M, Hoeflich A, Wolf E. Transgenic mouse models for studying the functions of insulin-like growth factor-binding proteins. FASEB J. 2000;14:629-40 pubmed..This review summarizes the current knowledge about the actions of IGFBPs in vivo based on the presently established transgenic mice. ..
- Ning Y, Schuller A, Bradshaw S, Rotwein P, Ludwig T, Frystyk J, et al. Diminished growth and enhanced glucose metabolism in triple knockout mice containing mutations of insulin-like growth factor binding protein-3, -4, and -5. Mol Endocrinol. 2006;20:2173-86 pubmed
- Childress P, Stayrook K, Alvarez M, Wang Z, Shao Y, Hernandez Buquer S, et al. Genome-Wide Mapping and Interrogation of the Nmp4 Antianabolic Bone Axis. Mol Endocrinol. 2015;29:1269-85 pubmed publisher..These data suggest that Nmp4 suppresses bone anabolism, in part, by regulating IGF-binding protein expression. Changes in Nmp4 status may lead to improvements in osteoprogenitor response to therapeutic cues. ..
- Cerro J, Grewal A, Wood T, Pintar J. Tissue-specific expression of the insulin-like growth factor binding protein (IGFBP) mRNAs in mouse and rat development. Regul Pept. 1993;48:189-98 pubmed..IGFBP-6 is expressed in the liver by e14, and also by a previously unrecognized cell population surrounding developing cartilage. Taken together these observations suggest distinct roles in development for each of the IGFBPs. ..
- Schuller A, Groffen C, van Neck J, Zwarthoff E, Drop S. cDNA cloning and mRNA expression of the six mouse insulin-like growth factor binding proteins. Mol Cell Endocrinol. 1994;104:57-66 pubmed..Finally, tissue-specific expression of the six mouse IGFBP genes was observed in adult tissues suggesting different roles or modes of actions in adult life. ..
- Chander H, Halpern M, Resnick Silverman L, Manfredi J, Germain D. Skp2B overexpression alters a prohibitin-p53 axis and the transcription of PAPP-A, the protease of insulin-like growth factor binding protein 4. PLoS ONE. 2011;6:e22456 pubmed publisher..Therefore, these findings indicate that the defect in p53 function and the increased proteolysis of IGFBP-4, we had observed, represent two components of the same pathway, which contributes to the oncogenic function of Skp2B. ..
- Austin K, Imam N, Pintar J, Brubaker P. IGF binding protein-4 is required for the growth effects of glucagon-like peptide-2 in murine intestine. Endocrinology. 2015;156:429-36 pubmed publisher..05). Collectively, these results indicate that the IGF-I-modulating protein, IGFBP-4, exerts a negative effect on basal intestinal growth but plays a positive regulatory role in the intestinotropic actions of GLP-2. ..
- Williams T, Williams M, Kuick R, Misek D, McDonagh K, Hanash S, et al. Candidate downstream regulated genes of HOX group 13 transcription factors with and without monomeric DNA binding capability. Dev Biol. 2005;279:462-80 pubmed..For two candidates, Igfbp4 and Fstl, interdigital limb bud expression was reduced in Hoxa13 mutants...
- Li Y, Arkins S, McCusker R, Donovan S, Liu Q, Jayaraman S, et al. Macrophages synthesize and secrete a 25-kilodalton protein that binds insulin-like growth factor-I. J Immunol. 1996;156:64-72 pubmed
- Zhang M, Smith E, Kuroda H, Banach W, Chernausek S, Fagin J. Targeted expression of a protease-resistant IGFBP-4 mutant in smooth muscle of transgenic mice results in IGFBP-4 stabilization and smooth muscle hypotrophy. J Biol Chem. 2002;277:21285-90 pubmed..Thus, IGFBP-4.7A results in greater growth inhibition than equivalent levels of native IGFBP-4 in vivo, demonstrating a role for IGFBP-4 proteolysis in the regulation of IGF-I action. ..
- Coschigano K, Holland A, Riders M, List E, Flyvbjerg A, Kopchick J. Deletion, but not antagonism, of the mouse growth hormone receptor results in severely decreased body weights, insulin, and insulin-like growth factor I levels and increased life span. Endocrinology. 2003;144:3799-810 pubmed..Finally, life span was significantly extended for the GHR -/- mice but remained unchanged for GHA dwarfs. These results suggest that the degree of blockade of GH signaling can lead to dramatically different phenotypes. ..
- Wood T, Rogler L, Czick M, Schuller A, Pintar J. Selective alterations in organ sizes in mice with a targeted disruption of the insulin-like growth factor binding protein-2 gene. Mol Endocrinol. 2000;14:1472-82 pubmed..These results demonstrate that up-regulation of multiple IGFBPs accompanies the absence of IGFBP-2 and that IGFBP-2 has a critical role, either directly or indirectly, in modulating spleen and liver size. ..
- Cederquist G, Azim E, Shnider S, Padmanabhan H, Macklis J. Lmo4 establishes rostral motor cortex projection neuron subtype diversity. J Neurosci. 2013;33:6321-32 pubmed publisher..Together, these results identify Lmo4 as a central developmental control over the diversity of motor cortex projection neuron subpopulations, establishing their area-specific identity and specialized connectivity. ..
- Glantschnig H, Varga F, Luegmayr E, Klaushofer K. Characterization of the mouse insulin-like growth factor binding protein 4 gene regulatory region and expression studies. DNA Cell Biol. 1998;17:51-60 pubmed..Studies on the intracellular transport by establishment of an IGFBP4/green fluorescent protein (GFP) fusion protein clearly demonstrate that IGFBP-4 is transported continuously along ..
- Lindenbergh Kortleve D, Rosato R, van Neck J, Nauta J, van Kleffens M, Groffen C, et al. Gene expression of the insulin-like growth factor system during mouse kidney development. Mol Cell Endocrinol. 1997;132:81-91 pubmed..IGFBP-3 mRNA was exclusively expressed in endothelial cells of the renal capillary system. Distinct mRNA expression for each member of the IGF system may point to specific roles in development and physiology of the mouse kidney. ..
- Hoerder Suabedissen A, Oeschger F, Krishnan M, Belgard T, Wang W, Lee S, et al. Expression profiling of mouse subplate reveals a dynamic gene network and disease association with autism and schizophrenia. Proc Natl Acad Sci U S A. 2013;110:3555-60 pubmed publisher..Our report emphasizes the importance of the study of transient features of the developing brain to better understand neurodevelopmental disorders. ..
- Zhang M, Faugere M, Malluche H, Rosen C, Chernausek S, Clemens T. Paracrine overexpression of IGFBP-4 in osteoblasts of transgenic mice decreases bone turnover and causes global growth retardation. J Bone Miner Res. 2003;18:836-43 pubmed..We attribute these effects to the sequestration of IGF-1 by IGFBP-4 and consequent impairment of IGF-1 action in skeletal tissue. ..
- Donahue L, Beamer W. Growth hormone deficiency in 'little' mice results in aberrant body composition, reduced insulin-like growth factor-I and insulin-like growth factor-binding protein-3 (IGFBP-3), but does not affect IGFBP-2, -1 or -4. J Endocrinol. 1993;136:91-104 pubmed..On the other hand, the changes in body protein are more likely to be effects of IGF-I.(ABSTRACT TRUNCATED AT 400 WORDS) ..
- Henemyre C, Markoff E. Decidualization and expression of insulin-like growth factor-I and insulin-like growth factor binding protein-4 in the periimplantation mouse uterus. Biol Reprod. 1998;58:801-6 pubmed..The restricted anatomical and temporal expression of IGF-I and IGFBP-4 mRNAs in the periimplantation uterus suggests a physiologic role for IGF-I and IGFBP-4 in the maintenance and expansion of decidualization. ..
- Mohan S, Baylink D, Pettis J. Insulin-like growth factor (IGF)-binding proteins in serum--do they have additional roles besides modulating the endocrine IGF actions?. J Clin Endocrinol Metab. 1996;81:3817-20 pubmed
- Maridas D, DeMambro V, Le P, Mohan S, Rosen C. IGFBP4 Is Required for Adipogenesis and Influences the Distribution of Adipose Depots. Endocrinology. 2017;158:3488-3500 pubmed publisherInsulinlike growth factor (IGF) I induces adipogenesis in vitro. IGF-binding protein 4 (IGFBP4) is highly expressed in adipocytes and osteoblasts and is inhibitory of IGFs in vitro...
- Maridas D, DeMambro V, Le P, Nagano K, Baron R, Mohan S, et al. IGFBP-4 regulates adult skeletal growth in a sex-specific manner. J Endocrinol. 2017;233:131-144 pubmed publisher..To test this, we comprehensively studied 8- and 16-week-old Igfbp4-/- mice...
- Boney C, Moats Staats B, Stiles A, D Ercole A. Expression of insulin-like growth factor-I (IGF-I) and IGF-binding proteins during adipogenesis. Endocrinology. 1994;135:1863-8 pubmed..The presence of a larger isoform of IGFBP-2 in a differentiation-dependent manner and a potentially novel IGFBP in response to IGF-I suggests that these IGFBPs may be important in modulating IGF-I action in adipogenesis. ..
- Shibata S, Fukuoka H, Sato R, Abe T, Suzuki Y. An in situ hybridization study of the insulin-like growth factor system in developing condylar cartilage of the fetal mouse mandible. Eur J Histochem. 2012;56:e23 pubmed publisher..These findings suggest that the IGF system is involved in the formation of the condylar cartilage as well as in the TMJ. ..
- Provenzano A, Besner G, James P, Harding P. Heparin-binding EGF-like growth factor (HB-EGF) overexpression in transgenic mice downregulates insulin-like growth factor binding protein (IGFBP)-3 and -4 mRNA. Growth Factors. 2005;23:19-31 pubmed..Overexpression of hHB-EGF affected the growth rate of these transgenic mice possibly through a pathway involving IGFBP-3 and IGFBP-4. ..
- Fernández Tornero C, Lozano R, Rivas G, Jiménez M, Ständker L, Díaz González D, et al. Synthesis of the blood circulating C-terminal fragment of insulin-like growth factor (IGF)-binding protein-4 in its native conformation. Crystallization, heparin and IGF binding, and osteogenic activity. J Biol Chem. 2005;280:18899-907 pubmed..Furthermore, it binds strongly to heparin, acquiring a well defined oligomeric structure that interacts with insulin-like growth factors, and promotes bone formation in cultures of murine calvariae. ..
- Guix M, Faber A, Wang S, Olivares M, Song Y, Qu S, et al. Acquired resistance to EGFR tyrosine kinase inhibitors in cancer cells is mediated by loss of IGF-binding proteins. J Clin Invest. 2008;118:2609-19 pubmed publisher..Moreover, combined therapeutic inhibition of EGFR and IGFIR may abrogate this acquired mechanism of drug resistance and is thus worthy of prospective clinical investigation. ..
- Schultz G, Hahnel A, Arcellana Panlilio M, Wang L, Goubau S, Watson A, et al. Expression of IGF ligand and receptor genes during preimplantation mammalian development. Mol Reprod Dev. 1993;35:414-20 pubmed..These findings suggest that the interactions of IGF ligands and receptors in preimplantation development might, indeed, be modulated by IGFPs.(ABSTRACT TRUNCATED AT 250 WORDS) ..
- Liu H, He Z, Tang Y, Mele C, Veeck L, Davis O, et al. Simultaneous detection of multiple gene expression in mouse and human individual preimplantation embryos. Fertil Steril. 1997;67:733-41 pubmed..This is the first report of the assessment of IGF family transcripts in individual embryos, and introduces a novel method for research and clinical diagnosis of preimplantation embryos. ..
- Bayol S, Brownson C, Loughna P. Electrical stimulation modulates IGF binding protein transcript levels in C2C12 myotubes. Cell Biochem Funct. 2005;23:361-5 pubmed..This study demonstrates that ES of muscle cells in vitro not only directly modulates the gene expression of contractile proteins but also modulates proteins that are part of the IGF regulatory system, in particular IGFBP-4. ..
- van Kleffens M, Groffen C, Rosato R, van den Eijnde S, van Neck J, Lindenbergh Kortleve D, et al. mRNA expression patterns of the IGF system during mouse limb bud development, determined by whole mount in situ hybridization. Mol Cell Endocrinol. 1998;138:151-61 pubmed..This supports the hypothesis that the IGF system may be involved in chondrogenic differentiation of mesenchyme and the regulation of apoptosis in the developing limb. ..
- Suzuki Y. Role of IGFBPs in the morphogenesis of lingual papillae. Anat Rec A Discov Mol Cell Evol Biol. 2005;286:841-7 pubmed..As previously suggested from a study on postnatal mice (Suzuki et al. J Comp Neurol 2005;482:74-84), IGFBP-4 acts in the epithelial invagination to form the trenches, grooves, or furrows of lingual papillae during development. ..
- Carter A, Nygard K, Mazzuca D, Han V. The expression of insulin-like growth factor and insulin-like growth factor binding protein mRNAs in mouse placenta. Placenta. 2006;27:278-90 pubmed..These findings suggest possible biological roles of the peptides at the feto-maternal interface. ..
- Bethel C, Vitullo J, Miller R, Aron D. Molecular cloning of mouse insulin-like growth factor binding protein 4 (IGFBP4) cDNA and expression of a fusion protein with IGF-binding activity. Biochem Mol Biol Int. 1994;34:385-92 pubmed..7 kD. An IGFBP-4/maltose binding protein fusion peptide expression in the pMal-p2 vector produced a fusion protein exhibiting both IGFBP immunoreactivity and IGF-I binding activity with specificity characteristic of IGFBPs. ..
- Glantschnig H, Varga F, Klaushofer K. Thyroid hormone and retinoic acid induce the synthesis of insulin-like growth factor-binding protein-4 in mouse osteoblastic cells. Endocrinology. 1996;137:281-6 pubmed..IGFBP-4, a known inhibitor of cellular proliferation, might contribute to the antiproliferative effect of T3 and retinoic acid on osteoblasts. ..
- Fraidenraich D, Stillwell E, Romero E, Wilkes D, Manova K, Basson C, et al. Rescue of cardiac defects in id knockout embryos by injection of embryonic stem cells. Science. 2004;306:247-52 pubmed..Thus, ES cells have the potential to reverse congenital defects through Id-dependent local and long-range effects in a mammalian embryo. ..
- Johnstone C, Tebbutt N, Abud H, White S, Stenvers K, Hall N, et al. Characterization of mouse A33 antigen, a definitive marker for basolateral surfaces of intestinal epithelial cells. Am J Physiol Gastrointest Liver Physiol. 2000;279:G500-10 pubmed..Thus the mA33 antigen appears to be a novel marker for both proliferating and differentiating intestinal epithelial cells...
- Schuller A, Zwarthoff E, Drop S. Gene expression of the six insulin-like growth factor binding proteins in the mouse conceptus during mid- and late gestation. Endocrinology. 1993;132:2544-50 pubmed..These data suggest that the different mIGFBPs might play distinct roles in mouse embryonal and fetal life. ..
- Tehrani M, Mumby M, Kamibayashi C. Identification of a novel protein phosphatase 2A regulatory subunit highly expressed in muscle. J Biol Chem. 1996;271:5164-70 pubmed..The nuclear localization of expressed B'alpha suggests that some variants of the B' subunit are involved in the nuclear functions of PP2A. ..
- Molyneaux B, Arlotta P, Hirata T, Hibi M, Macklis J. Fezl is required for the birth and specification of corticospinal motor neurons. Neuron. 2005;47:817-31 pubmed
- Kleffens M, Groffen C, Neck J, Vermeij Keers C, Drop S. mRNA and protein localization of the IGF system during mouse embryonic development in areas with apoptosis. Growth Horm IGF Res. 1999;9:195-204 pubmed..Tissue-specific modulation of IGF protective action against apoptosis by the different IGFBPs during mouse embryonal development may contribute to organ specific morphology. ..
- Donahue L, Watson G, Beamer W. Regulation of metabolic water and protein compartments by insulin-like growth factor-I and testosterone in growth hormone-deficient lit/lit mice. J Endocrinol. 1993;139:431-9 pubmed..Independent effects were induced by each hormone alone for kidney and spleen weight, kidney and spleen protein content and BUN.(ABSTRACT TRUNCATED AT 250 WORDS) ..
- Conover C, Bale L, Overgaard M, Johnstone E, Laursen U, Füchtbauer E, et al. Metalloproteinase pregnancy-associated plasma protein A is a critical growth regulatory factor during fetal development. Development. 2004;131:1187-94 pubmed..IGF bioavailability and mitogenic effectiveness in vitro through regulated cleavage of IGF-binding protein 4 (IGFBP4). To determine its function in vivo, we generated PAPPA-null mice by gene targeting...
- Arnold P, Ma J, Citron B, Zoubine M, Festoff B. Selective developmental regulation of gene expression for insulin-like growth factor-binding proteins in mouse spinal cord. Spine (Phila Pa 1976). 2000;25:1765-70 pubmed..Both IGFBP-2 and BP-5 are developmentally regulated in mouse spinal cord, with higher levels of those at early embryonic stages indicating their potential role in development of the mouse spinal cord. ..
- Okano T, Kelley M. Expression of insulin-like growth factor binding proteins during mouse cochlear development. Dev Dyn. 2013;242:1210-21 pubmed publisher..These data suggest that IGFBPs may act to precisely regulate activation of IGF signaling in the developing cochlea in a cell type-specific manner, contributing to cellular patterning and differentiation in the cochlea. ..
- Kang D, Chung Y, Lee J, Bang J, Kim D, Kim S, et al. Immunohistochemical study on the distribution of insulin-like growth factor-binding protein 4 in the central nervous system of SOD1(G93A) transgenic mice as an in vivo model of amyotrophic lateral sclerosis. Ann Anat. 2008;190:502-9 pubmed publisher..performed immunohistochemical studies to investigate the changes of insulin-like growth factor-binding protein 4 (IGFBP4) in the central nervous system...
- Woo D, Kurtz I. Mapping blood pressure loci in (A/J x B6)F2 mice. Physiol Genomics. 2003;15:236-42 pubmed..Defining the molecular differences between the A/J and the B6 alleles at these novel loci with major influences on the BP phenotype will contribute to our understanding of the complex genetics of BP control. ..
- Henemyre C, Markoff E. Expression of insulin-like growth factor binding protein-4, insulin-like growth factor-I receptor, and insulin-like growth factor-I in the mouse uterus throughout the estrous cycle. Mol Reprod Dev. 1999;52:350-9 pubmed..They also suggest that IGFBP-4 may play a role in uterine physiology independent of the inhibition of IGF-I action, and that IGF-IR is constitutively expressed in the mouse uterus. ..