Insulinoliki faktor rasta 2

Insulinoliki faktor rasta 2
Dostupne strukture
PDB	Pretraga ortologa: PDBe RCSB
Spisak PDB ID kodova
	3KR3, 1IGL, 2L29, 2V5P, 3E4Z
Identifikatori
Aliasi	IGF2
Vanjski ID-jevi	OMIM: 147470 MGI: 96434 HomoloGene: 510 GeneCards: IGF2
Lokacija gena (čovjek)
Hrom.	Hromosom 11 (čovjek)
Kraj	2,158,391 bp
Lokacija gena (miš)
Hrom.	Hromosom 7 (miš)
Kraj	142,220,553 bp
Obrazac RNK ekspresije
	; ; ; ;
	Više referentnih podataka o ekspresiji
Ontologija gena
Molekularna funkcija	• insulin receptor binding; • hormone activity; • GO:0001948, GO:0016582 vezivanje za proteine; • growth factor activity; • insulin-like growth factor receptor binding; • integrin binding; • protein serine/threonine kinase activator activity; • receptor ligand activity;
Ćelijska komponenta	• extracellular region; • platelet alpha granule lumen; • Vanćelijsko;
Biološki proces	• regulation of gene expression by genetic imprinting; • skeletal system development; • GO:1901047 insulin receptor signaling pathway; • positive regulation of protein kinase B signaling; • GO:0009373 regulation of transcription, DNA-templated; • ossification; • platelet degranulation; • multicellular organism development; • glucose metabolic process; • positive regulation of mitotic nuclear division; • positive regulation of cell division; • positive regulation of MAPK cascade; • positive regulation of activated T cell proliferation; • positive regulation of protein serine/threonine kinase activity; • carbohydrate metabolic process; • regulation of signaling receptor activity; • GO:1901227 negative regulation of transcription by RNA polymerase II; • osteoblast differentiation; • in utero embryonic development; • embryonic placenta development; • positive regulation of protein phosphorylation; • positive regulation of cell population proliferation; • animal organ morphogenesis; • exocrine pancreas development; • GO:0033127, GO:2000281, GO:2000817 regulation of histone modification; • insulin receptor signaling pathway via phosphatidylinositol 3-kinase; • positive regulation of multicellular organism growth; • GO:0048554 positive regulation of catalytic activity; • positive regulation of glycogen biosynthetic process; • GO:0003257, GO:0010735, GO:1901228, GO:1900622, GO:1904488 positive regulation of transcription by RNA polymerase II; • GO:1903106 positive regulation of insulin receptor signaling pathway; • positive regulation of peptidyl-tyrosine phosphorylation; • striated muscle cell differentiation; • regulation of muscle cell differentiation; • embryonic placenta morphogenesis; • positive regulation of glycogen (starch) synthase activity;
	Izvori:Amigo / QuickGO
Ortolozi
	3481
	16002
	ENSG00000167244
	ENSMUSG00000048583
	P01344
	P09535
	NM_001291862; NM_000612; NM_001007139; NM_001127598; NM_001291861
	NM_001122736; NM_001122737; NM_010514; NM_001315488; NM_001315489
	NP_000603; NP_001007140; NP_001121070; NP_001278790; NP_001278791
	NP_001116208; NP_001116209; NP_001302417; NP_001302418; NP_034644
	Wikipodaci
Pogledaj/uredi – čovjek	Pogledaj/uredi – miš

Insulinoliki faktor rasta 2 (IGF-2), jedan je od tri proteinska hormon koji imaju strukturnu sličnost sa insulinom. Definicija MeSH glasi: "Dobro karakterizirani neutralni peptid za koji se vjeruje da ga jetra luči i da cirkulira u krvi. Ima aktivnosti regulacije rasta, slične insulinu i mitogenima. Faktor rasta ima glavnu ulogu, ali ne i apsolutnu, ovisno o somatotropinu. Vjeruje se da je glavni faktor rasta i fetusa, za razliku od insulinolikog faktor rasta 1, koji je glavni faktor rasta kod odraslih"^[5]

Struktura gena[uredi | uredi izvor]

Kod ljudi, gen IGF2 nalazi se na hromosomu 11, pozicija: p15.5, regionu koji sadrži brojne imprintirane gene. Kod miševa se ova homologna regija nalazi u distalnokraju hromosoma 7. U oba organizma utisnut je recesivni Igf2, s izrazom koji povoljno rezultira od očeva naslijeđenog alela. Međutim, u nekim regijama ljudskog mozga dolazi do gubitka utiskivanja što rezultira transkripcijom IGF2 i H19 iz oba roditeljska alela.^[6]

Protein CTCF je uključen u potiskivanje ekspresije gena, vezujući se za H19, kontrolnu regiju za imprintiranje (ICR) zajedno sa diferencijalno-metiliranom regijom - 1 (DMR1) i regijom za pričvršćivanje matrice −3 (MAR3). Ove tri sekvence DNK vežu se za CTCF na način koji ograničava pristup nižeg pojačivača u regiju Igf2. Mehanizam u kojem se CTCF veže za ove regije još ji'nije poznat, ali može uključivati ili izravnu interakciju DNK-CTCF ili mogu biti posredovani drugim proteinima. Kod sisara (miševi, ljudi, svinje), aktivan je samo alel insulinlikog faktora rasta (IGF2), naslijeđenog od oca; ono što je naslijeđeno od majke nije - fenomen koji se naziva imprinting ili nutiskivanje. Mehanizam: alel majke ima izolator između IGF2 promotora i pojačivača. Kao i alel oca, ali u njegovom slučaju izolator je metiliran. CTCF se više ne može vezati za izolator, pa je pojačivač sada slobodan uključiti očev promotor IGF2.^[7]

Funkcija[uredi | uredi izvor]

Glavna uloga IGF-2 je da djelujue kao hormon za poticanje rasta tokom gestacije.

IGF-2 vrši svoje efekte vezanjem za IGF-1 receptor i za kratku izoformu insulinskog receptora (IR-A ili egzon 11.^[8] IGF2 se također može vezati za IGF-2 receptor (koji se naziva i kation-nezavisni manoza 6-fosfatni receptor), koji deluje kao signalni antagonist, odnosno spriječave IGF2 odgovore. 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.

IGF2 se također može vezati za IGF-2 receptor (koji se naziva i kation-neovisni manozni 6-fosfatni receptor), koji deluje kao signalni antagonist; odnosno spriječiti IGF2 odgovore.

U procesu folikulogeneze, teka-ćelije stvaraju IGF-2 da djeluje na autokrini način na same ćelije-teka, a na parakrini način na ćelije granuloze u jajniku.^{[nedostaje referenca]} IGF2 promovira proliferaciju granuloznih ćelija tokom folikulske faze menstruacijskog ciklusa, djelujući zajedno s folikul-stimulirajućim hormonom (FSH).^[9] Nakon ovulacije, IGF-2 pospješuje lučenje progesterona, tokom luteusne faze menstrucijskosđg ciklusa , zajedno sa luteinizirajućim hormonom (LH). Dakle, IGF2 djeluje kao ko-hormon zajedno s FSH i LH.^[10]

Studija na Medicinskom fakultetu Mount Sinai (Mount Sinai School of Medicine), otkrila je da IGF-2 može biti povezan sa pamćenjem i reprodukcijom.^[11]^[12]

Klinička relevantnost[uredi | uredi izvor]

Ponekad se proizvodi u prekomjernoj količini u otočićnim ćelijama tumora i neotočnih hipoglikemijskih tumora, uzrokujući hipoglikemiju. Doege-Potterov sindrom je paraneoplazijski sindrom^[13] kod kojeg je hipoglikemija povezana sa prisustvom jednog ili više vlaknastih tumora, koji nisu na otočićima u pleuraskoj šupljini. Gubitak utiskivanja IGF2 je uobičajena karakteristika tumora viđenih u poremaćaju zvanom Beckwith-Wiedemannov sindrom. .Kako IGF2 pospješuje razvoj beta-ćelija fetusne gušterače, vjeruje se da je povezan sa nekim oblicima dijabetes melitusa. Preeklampsija inducira smanjenje nivoa metilacije u IGF2 demetiliranoj regiji, a to bi mogao biti jedan od mehanizama koji stoje iza povezanosti između intrauterine izloženosti preeklampsiji i visokog rizika za metaboličke bolesti u kasnijem životu dojenčadi.^[14]

Interakcije[uredi | uredi izvor]

Pokazano je da insulinoliki faktor rasta interakcija protein-proteinu intrakciji sa IGFBP3.^[15]^[16]^[17]^[18] i transferinom.^[15]

Također pogledajte[uredi | uredi izvor]

Reference[uredi | uredi izvor]

^ ^a ^b ^c GRCh38: Ensembl release 89: ENSG00000167244 - Ensembl, maj 2017
^ ^a ^b ^c GRCm38: Ensembl release 89: ENSMUSG00000048583 - Ensembl, maj 2017
^ "Human PubMed Reference:". National Center for Biotechnology Information, U.S. National Library of Medicine.
^ "Mouse PubMed Reference:". National Center for Biotechnology Information, U.S. National Library of Medicine.
^ "Insulin-Like Growth Factor II". MeSH. NCBI.
^ Pham NV, Nguyen MT, Hu JF, Vu TH, Hoffman AR (Nov 1998). "Dissociation of IGF2 and H19 imprinting in human brain". Brain Research. 810 (1–2): 1–8. doi:10.1016/s0006-8993(98)00783-5. PMID 9813220.
^ Russell, Peter J. (2009). iGenetics: A Molecular Approach (3rd izd.). Upper Saddle River, N.J.: Pearson Education. str. 533. ISBN 978-0-321-61022-5. Nepoznati parametar |name-list-format= zanemaren (prijedlog zamjene: |name-list-style=) (pomoć)
^ Frasca F, Pandini G, Scalia P, Sciacca L, Mineo R, Costantino A, Goldfine ID, Belfiore A, Vigneri R (1999). "Insulin receptor isoform A, a newly recognized, high-affinity insulin-like growth factor II receptor in fetal and cancer cells". Molecular and Cellular Biology. 19 (5): 3278–88. doi:10.1128/MCB.19.5.3278. PMC 84122. PMID 10207053.
^ Neidhart, M (2016). DNA Methylation and Complex Human Disease (1st izd.). San Diego: Academic Press. str. 222. ISBN 9780124201941.
^ Neidhart, M (2016). DNA Methylation and Complex Human Disease (1st izd.). San Diego: Academic Press. str. 22. ISBN 978-0124201941.
^ Chen DY, Stern SA, Garcia-Osta A, Saunier-Rebori B, Pollonini G, Bambah-Mukku D, Blitzer RD, Alberini CM (Jan 2011). "A critical role for IGF-II in memory consolidation and enhancement". Nature. 469 (7331): 491–7. doi:10.1038/nature09667. PMC 3908455. PMID 21270887.
^ 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 (Oct 2011). "A hippocampal insulin-growth factor 2 pathway regulates the extinction of fear memories". The EMBO Journal. 30 (19): 4071–83. doi:10.1038/emboj.2011.293. PMC 3209781. PMID 21873981.
^ Balduyck B, Lauwers P, Govaert K, Hendriks J, De Maeseneer M, Van Schil P (Jul 2006). "Solitary fibrous tumor of the pleura with associated hypoglycemia: Doege-Potter syndrome: a case report". Journal of Thoracic Oncology. 1 (6): 588–90. doi:10.1097/01243894-200607000-00016. PMID 17409923.
^ He J, Zhang A, Fang M, Fang R, Ge J, Jiang Y, Zhang H, Han C, Ye X, Yu D, Huang H, Liu Y, Dong M (12. 7. 2013). "Methylation levels at IGF2 and GNAS DMRs in infants born to preeclamptic pregnancies". BMC Genomics. 14: 472. doi:10.1186/1471-2164-14-472. PMC 3723441. PMID 23844573.
^ ^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 Letters. 509 (3): 395–8. doi:10.1016/S0014-5793(01)03204-5. PMID 11749962.
^ Buckway CK, Wilson EM, Ahlsén M, Bang P, Oh Y, Rosenfeld RG (Oct 2001). "Mutation of three critical amino acids of the N-terminal domain of IGF-binding protein-3 essential for high affinity IGF binding". The Journal of Clinical Endocrinology and Metabolism. 86 (10): 4943–50. doi:10.1210/jcem.86.10.7936. PMID 11600567.
^ Twigg SM, Baxter RC (Mar 1998). "Insulin-like growth factor (IGF)-binding protein 5 forms an alternative ternary complex with IGFs and the acid-labile subunit". The Journal of Biological Chemistry. 273 (11): 6074–9. doi:10.1074/jbc.273.11.6074. PMID 9497324.
^ Firth SM, Ganeshprasad U, Baxter RC (Jan 1998). "Structural determinants of ligand and cell surface binding of insulin-like growth factor-binding protein-3". The Journal of Biological Chemistry. 273 (5): 2631–8. doi:10.1074/jbc.273.5.2631. PMID 9446566.

Dopunska literatura[uredi | uredi izvor]

O'Dell SD, Day IN (Jul 1998). "Insulin-like growth factor II (IGF-II)". The International Journal of Biochemistry & Cell Biology. 30 (7): 767–71. doi:10.1016/S1357-2725(98)00048-X. PMID 9722981.
Butler AA, Yakar S, Gewolb IH, Karas M, Okubo Y, LeRoith D (Sep 1998). "Insulin-like growth factor-I receptor signal transduction: at the interface between physiology and cell biology". Comparative Biochemistry and Physiology B. 121 (1): 19–26. doi:10.1016/S0305-0491(98)10106-2. PMID 9972281.
Kalli KR, Conover CA (maj 2003). "The insulin-like growth factor/insulin system in epithelial ovarian cancer". Frontiers in Bioscience. 8 (4): d714–22. doi:10.2741/1034. PMID 12700030.
Wood AW, Duan C, Bern HA (2005). Insulin-like growth factor signaling in fish. International Review of Cytology. 243. str. 215–85. doi:10.1016/S0074-7696(05)43004-1. ISBN 9780123646477. PMID 15797461.
Fowden AL, Sibley C, Reik W, Constancia M (2006). "Imprinted genes, placental development and fetal growth". Hormone Research. 65 Suppl 3 (3): 50–8. doi:10.1159/000091506. PMID 16612114.

Vanjski linkovi[uredi | uredi izvor]

Insulin-Like Growth Factor II na US National Library of Medicine Medical Subject Headings (MeSH)

Commons logo

Commons ima datoteke na temu: Insulinoliki faktor rasta 2

[refGRCh38Ensembl-1] GRCh38: Ensembl release 89: ENSG00000167244 - Ensembl, maj 2017

[refGRCm38Ensembl-2] GRCm38: Ensembl release 89: ENSMUSG00000048583 - Ensembl, maj 2017

[3] "Human PubMed Reference:". National Center for Biotechnology Information, U.S. National Library of Medicine.

[4] "Mouse PubMed Reference:". National Center for Biotechnology Information, U.S. National Library of Medicine.

[5] "Insulin-Like Growth Factor II". MeSH. NCBI.

[6] Pham NV, Nguyen MT, Hu JF, Vu TH, Hoffman AR (Nov 1998). "Dissociation of IGF2 and H19 imprinting in human brain". Brain Research. 810 (1–2): 1–8. doi:10.1016/s0006-8993(98)00783-5. PMID 9813220.

[7] Russell, Peter J. (2009). iGenetics: A Molecular Approach (3rd izd.). Upper Saddle River, N.J.: Pearson Education. str. 533. ISBN 978-0-321-61022-5. Nepoznati parametar |name-list-format= zanemaren (prijedlog zamjene: |name-list-style=) (pomoć)

[pmid10207053-8] Frasca F, Pandini G, Scalia P, Sciacca L, Mineo R, Costantino A, Goldfine ID, Belfiore A, Vigneri R (1999). "Insulin receptor isoform A, a newly recognized, high-affinity insulin-like growth factor II receptor in fetal and cancer cells". Molecular and Cellular Biology. 19 (5): 3278–88. doi:10.1128/MCB.19.5.3278. PMC 84122. PMID 10207053.

[9] Neidhart, M (2016). DNA Methylation and Complex Human Disease (1st izd.). San Diego: Academic Press. str. 222. ISBN 9780124201941.

[10] Neidhart, M (2016). DNA Methylation and Complex Human Disease (1st izd.). San Diego: Academic Press. str. 22. ISBN 978-0124201941.

[11] Chen DY, Stern SA, Garcia-Osta A, Saunier-Rebori B, Pollonini G, Bambah-Mukku D, Blitzer RD, Alberini CM (Jan 2011). "A critical role for IGF-II in memory consolidation and enhancement". Nature. 469 (7331): 491–7. doi:10.1038/nature09667. PMC 3908455. PMID 21270887.

[pmid21873981-12] 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 (Oct 2011). "A hippocampal insulin-growth factor 2 pathway regulates the extinction of fear memories". The EMBO Journal. 30 (19): 4071–83. doi:10.1038/emboj.2011.293. PMC 3209781. PMID 21873981.

[pmid17409923-13] Balduyck B, Lauwers P, Govaert K, Hendriks J, De Maeseneer M, Van Schil P (Jul 2006). "Solitary fibrous tumor of the pleura with associated hypoglycemia: Doege-Potter syndrome: a case report". Journal of Thoracic Oncology. 1 (6): 588–90. doi:10.1097/01243894-200607000-00016. PMID 17409923.

[pmid573-14] He J, Zhang A, Fang M, Fang R, Ge J, Jiang Y, Zhang H, Han C, Ye X, Yu D, Huang H, Liu Y, Dong M (12. 7. 2013). "Methylation levels at IGF2 and GNAS DMRs in infants born to preeclamptic pregnancies". BMC Genomics. 14: 472. doi:10.1186/1471-2164-14-472. PMC 3723441. PMID 23844573.

[pmid11749962-15] 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 Letters. 509 (3): 395–8. doi:10.1016/S0014-5793(01)03204-5. PMID 11749962.

[pmid11600567-16] Buckway CK, Wilson EM, Ahlsén M, Bang P, Oh Y, Rosenfeld RG (Oct 2001). "Mutation of three critical amino acids of the N-terminal domain of IGF-binding protein-3 essential for high affinity IGF binding". The Journal of Clinical Endocrinology and Metabolism. 86 (10): 4943–50. doi:10.1210/jcem.86.10.7936. PMID 11600567.

[pmid9497324-17] Twigg SM, Baxter RC (Mar 1998). "Insulin-like growth factor (IGF)-binding protein 5 forms an alternative ternary complex with IGFs and the acid-labile subunit". The Journal of Biological Chemistry. 273 (11): 6074–9. doi:10.1074/jbc.273.11.6074. PMID 9497324.

[pmid9446566-18] Firth SM, Ganeshprasad U, Baxter RC (Jan 1998). "Structural determinants of ligand and cell surface binding of insulin-like growth factor-binding protein-3". The Journal of Biological Chemistry. 273 (5): 2631–8. doi:10.1074/jbc.273.5.2631. PMID 9446566.

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