Insulin-like growth factor 2
Insulin-like growth factor 2 (IGF-2) is one of three protein hormones that share structural similarity to insulin.
Gene structure
In humans, the IGF2 gene is located on chromosome 11p15.5, a region which contains numerous imprinted genes. In mice this homologous region is found at distal chromosome 7. In both organisms, Igf2 is imprinted, with expression resulting favourably from the paternally inherited allele.
The protein CTCF is involved in repressing expression of the gene, by binding to the H19 imprinting control region (ICR) along with Differentially-methylated Region-1 (DMR1) and Matrix Attachment Region -3 (MAR3). These three DNA sequences bind to CTCF in a way that limits downstream enhancer access to the Igf2 region. The mechanism in which CTCF binds to these regions is currently unknown, but could include either a direct DNA-CTCF interaction or it could possibly be mediated by other proteins
IGF-2 exerts its effects by binding to the IGF-1 receptor. IGF2 may also bind to the IGF-2 receptor (also called the cation-independent mannose 6-phosphate receptor), which acts as a signalling antagonist; that is, to prevent IGF2 responses.
Function
The major role of IGF2 is as a growth promoting hormone during gestation.
IGF-2 exerts its effects by binding to the IGF-1 receptor. IGF2 may also bind to the IGF-2 receptor (also called the cation-independent mannose 6-phosphate receptor), which acts as a signalling antagonist; that is, to prevent IGF2 responses.
In the process of Folliculogenesis, IGF2 is created by Theca cells to act in an autocrine manner on the theca cells themselves, and in a paracrine manner on Granulosa cells in the ovary. IGF2 promotes granulosa cell proliferation during the follicular phase of the menstrual cycle, acting alongside Follicle Stimulating Hormone (FSH). After ovulation has occurred, IGF-2 promotes progesterone secretion during the luteal phase of the menstrual cycle together with Luteinizing Hormone (LH). Thus, IGF2 acts as a Co-hormone together with both FSH and LH.
A study at the Mount Sinai School of Medicine found that IGF-II may be linked to memory.[1] The study found that it may play a key role in memory and could potentially be used to treat Alzheimer's Disease.[2][3]. A study at the European Neuroscience Institute-Goettingen (Germany) found that fear extinction-induced IGF2/IGFBP7 signalling promotes the survival of 17–19-day-old newborn hippocampal neurons. This suggests that therapeutic strategies that enhance IGF2 signalling and adult neurogenesis might be suitable to treat diseases linked to excessive fear memory such as PTSD.[4]
Diseases
It is sometimes produced in excess in islet cell tumours, causing hypoglycemia. Doege-Potter syndrome is a paraneoplastic syndrome[5] in which hypoglycemia is associated with the presence of one or more non-islet fibrous tumors in the pleural cavity. Loss of imprinting of IGF2 is a common feature in tumours seen in Beckwith-Wiedeman syndrome.it also works on beta cells of pancreas which is responsible for diabetus mallitus
Interactions
Insulin-like growth factor 2 has been shown to interact with IGFBP3[6][7][8][9] and Transferrin.[6]
See also
References
- ^ http://www.nature.com/nature/journal/v469/n7331/full/nature09667.html
- ^ "Brain chemical could treat Alzheimer's". The Times Of India. http://timesofindia.indiatimes.com/life-style/health-fitness/health/Brain-chemical-could-treat-Alzheimers/articleshow/7371086.cms.
- ^ MacRae, Fiona (27 January 2011). "Scientists find key chemical that could boost memory and end the misery of Alzheimer's". Daily Mail (London). http://www.dailymail.co.uk/health/article-1350791/Alzheimers-Scientists-key-chemical-IGF-II-boost-memory.html.
- ^ http://www.nature.com/emboj/journal/vaop/ncurrent/full/emboj2011293a.html
- ^ Balduyck B, Lauwers P, Govaert K, Hendriks J, De Maeseneer M, Van Schil P (July 2006). "Solitary fibrous tumor of the pleura with associated hypoglycemia: Doege-Potter syndrome: a case report". J Thorac Oncol 1 (6): 588–90. doi:10.1097/01243894-200607000-00016. PMID 17409923.
- ^ a b Storch, S; Kübler B, Höning S, Ackmann M, Zapf J, Blum W, Braulke T (Dec. 2001). "Transferrin binds insulin-like growth factors and affects binding properties of insulin-like growth factor binding protein-3". FEBS Lett. (Netherlands) 509 (3): 395–8. doi:10.1016/S0014-5793(01)03204-5. ISSN 0014-5793. PMID 11749962.
- ^ Buckway, C K; Wilson E M, Ahlsén M, Bang P, Oh Y, Rosenfeld R G (Oct. 2001). "Mutation of three critical amino acids of the N-terminal domain of IGF-binding protein-3 essential for high affinity IGF binding". J. Clin. Endocrinol. Metab. (United States) 86 (10): 4943–50. doi:10.1210/jc.86.10.4943. ISSN 0021-972X. PMID 11600567.
- ^ Twigg, S M; Baxter R C (Mar. 1998). "Insulin-like growth factor (IGF)-binding protein 5 forms an alternative ternary complex with IGFs and the acid-labile subunit". J. Biol. Chem. (UNITED STATES) 273 (11): 6074–9. doi:10.1074/jbc.273.11.6074. ISSN 0021-9258. PMID 9497324.
- ^ Firth, S M; Ganeshprasad U, Baxter R C (Jan. 1998). "Structural determinants of ligand and cell surface binding of insulin-like growth factor-binding protein-3". J. Biol. Chem. (UNITED STATES) 273 (5): 2631–8. doi:10.1074/jbc.273.5.2631. ISSN 0021-9258. PMID 9446566.
External links
Further reading
- O'Dell SD, Day IN (1998). "Insulin-like growth factor II (IGF-II).". Int. J. Biochem. Cell Biol. 30 (7): 767–71. doi:10.1016/S1357-2725(98)00048-X. PMID 9722981.
- Butler AA, Yakar S, Gewolb IH, et al. (1999). "Insulin-like growth factor-I receptor signal transduction: at the interface between physiology and cell biology.". Comp. Biochem. Physiol. B, Biochem. Mol. Biol. 121 (1): 19–26. doi:10.1016/S0305-0491(98)10106-2. PMID 9972281.
- Kalli KR, Conover CA (2004). "The insulin-like growth factor/insulin system in epithelial ovarian cancer.". Front. Biosci. 8: d714–22. doi:10.2741/1034. PMID 12700030.
- Wood AW, Duan C, Bern HA (2005). "Insulin-like growth factor signaling in fish.". Int. Rev. Cytol. 243: 215–85. doi:10.1016/S0074-7696(05)43004-1. PMID 15797461.
- Fowden AL, Sibley C, Reik W, Constancia M (2006). "Imprinted genes, placental development and fetal growth.". Horm. Res. 65 Suppl 3 (3): 50–8. doi:10.1159/000091506. PMID 16612114.
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PDB gallery
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1igl: SOLUTION STRUCTURE OF HUMAN INSULIN-LIKE GROWTH FACTOR II RELATIONSHIP TO RECEPTOR AND BINDING PROTEIN INTERACTIONS
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| Fibroblast |
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| EGF-like domain |
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| TGFβ pathway |
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| Insulin-like |
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| Platelet-derived |
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| Vascular endothelial |
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| Other |
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B trdu: iter (nrpl/grfl/cytl/horl), csrc (lgic, enzr, gprc, igsr, intg, nrpr/grfr/cytr), itra (adap, gbpr, mapk), calc, lipd; path (hedp, wntp, tgfp+mapp, notp, jakp, fsap, hipp, tlrp)
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