Insulin-like growth factor 2

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Insulin-like growth factor 2 (somatomedin A)
Protein IGF2 PDB 1igl.png
PDB rendering based on 1igl.
Available structures
PDB Ortholog search: PDBe, RCSB
Identifiers
Symbols IGF2 ; C11orf43; IGF-II; PP9974
External IDs OMIM147470 MGI96434 HomoloGene510 GeneCards: IGF2 Gene
RNA expression pattern
PBB GE IGF2 202409 at tn.png
PBB GE IGF2 202410 x at tn.png
PBB GE IGF2 210881 s at tn.png
More reference expression data
Orthologs
Species Human Mouse
Entrez 3481 16002
Ensembl ENSG00000167244 ENSMUSG00000048583
UniProt P01344 P09535
RefSeq (mRNA) NM_000612 NM_001122736
RefSeq (protein) NP_000603 NP_001116208
Location (UCSC) Chr 11:
2.15 – 2.18 Mb
Chr 7:
142.65 – 142.67 Mb
PubMed search [2] [3]
Insulin-like growth factor II E-peptide
Identifiers
Symbol IGF2_C
Pfam PF08365
InterPro IPR013576

Insulin-like growth factor 2 (IGF-2) is one of three protein hormones that share structural similarity to insulin. The MeSH definition reads: "A well-characterized neutral peptide believed to be secreted by the liver and to circulate in the blood. It has growth-regulating, insulin-like and mitogenic activities. The growth factor has a major, but not absolute, dependence on somatotropin. It is believed to be a major fetal growth factor in contrast to Insulin-like growth factor 1, which is a major growth factor in adults".1

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. However, in the human brain a loss of imprinting occurs resulting in both IGF2 and H19 being transcribed from both parental alleles.2

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. In mammals (mice, humans, pigs), only the allele for insulin-like growth factor-2 (IGF2) inherited from one's father is active; that inherited from the mother is not — a phenomenon called imprinting.The mechanism: the mother's allele has an insulator between the IGF2 promoter and enhancer. So does the father's allele, but in his case, the insulator has been methylated. CTCF can no longer bind to the insulator, and so the enhancer is now free to turn on the father's IGF2 promoter.citation needed

Function

The major role of IGF-2 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, IGF-2 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 ovarycitation needed. IGF2 promotes granulosa cell proliferation during the follicular phase of the menstrual cycle, acting alongside follicle stimulating hormone (FSH)citation needed. 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 LHcitation needed.

A study at the Mount Sinai School of Medicine found that IGF-2 may be linked to memory.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 syndrome5 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-Wiedemann syndrome. As IGF2 promotes development of fetal pancreatic beta cells, it is believed to be related to some forms of diabetes mellitus.

Interactions

Insulin-like growth factor 2 has been shown to interact with IGFBP36789 and Transferrin.6

See also

References

  1. ^ http://www.ncbi.nlm.nih.gov/mesh/68007335
  2. ^ [1]
  3. ^ Chen, Dillon; Sarah Stern; Ana Garcia-Osta; Bernadette Saunier-Rebori; Gabriella Pollonini; Dhananjay Bambah-Mukku; Robert D. Blitzer; Cristina M. Alberini (27 January 2011). "A critical role for IGF-II in memory consolidation and enhancement". Nature 469: 491–497. doi:10.1038/nature09667. 
  4. ^ Agis-Balboa RC, Arcos-Diaz D, Wittnam J, Govindarajan N, Blom K, Burkhardt S, Haladyniak U, Agbemenyah HY, Zovoilis A, Salinas-Riester G, Opitz L, Sananbenesi F, Fischer A (August 2011). "A hippocampal insulin-growth factor 2 pathway regulates the extinction of fear memories". EMBO J 30 (19): 4071–83. doi:10.1038/emboj.2011.293. PMC 3209781. PMID 21873981. 
  5. ^ 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. 
  6. ^ 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. 
  7. ^ 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/jcem.86.10.7936. ISSN 0021-972X. PMID 11600567. 
  8. ^ 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. 
  9. ^ 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.