CCL2

Hemokin (C-C motiv) ligand 2
	; PDB prikaz baziran na 1dok.
Dostupne strukture
	1dok, 1dol, 1dom, 1don, 1ml0, 2bdn
Identifikatori
Simboli	CCL2; GDCF-2; GDCF-2 HC11; HC11; HSMCR30; MCAF; MCP-1; MCP1; MGC9434; SCYA2; SMC-CF
Vanjski ID	OMIM: 158105 MGI: 98259 HomoloGene: 2245 GeneCards: CCL2 Gene
Ontologija gena
Molekularna funkcija	• aktivnost protein kinaza; • transdukcija signala; • chemokinska aktivnost;
Celularna komponenta	• ekstracelularni region; • ekstracelularni prostor; • membrana;
Biološki proces	• proteinska aminokiselinska fosforilacija; • ćelijska homeostaza kalcijum jona; • anti-apoptoza; • hemotaksa; • inflamatorni respons; • humoralni imunski respons; • ćelijska adhezija; • G-protein signalizacija, spregnuta sa ciklikličnim nukleotidnim drugim glasnikom; • JAK-STAT kaskada; • interćelijska signalizacija; • morfogeneza organa; • replikacija viralnog genoma;
Pregled RNK izražavanja
	podaci
Ortolozi

edit

CCL2, hemokin (C-C motiv) ligand 2, je mali citokin iz CC hemokin familije koji je takođe poznat kao monocit hemotaksni protein-1 (MCP-1), i mali induktivni citokin A2. CCL2 regrutira monocite, memorijske T ćelije, i dendritske ćelije na mesta povrede tkiva i infekcije.^[1]^[2]^[3]

Genomika

Kao i mnogi drugi CC hemokini, CCL2 je lociran na hromozomu 17 (17q11.2-q21.1) kod ljudi.^[4] Ovaj gen sadrži 1,927 baza i nalazi se na Vatson (plus) lancu. On ima tri eksona i dva introna. CCL2 nastaje kao proteinski prekurzor koji sadrži signalni peptid sa 23 aminokiseline i krajnji peptid sa 76 aminokiselina.^[5]^[6] Molekulska težina je 11.025 kDa. Mišji homolog je Sig-je.

Populaciona genetika

Nivoi ovog proteina značajno variraju kod normalnih ljudi. Multivarijabilna-prilagođena naslednost MCP-1 koncentracija kod ljudi evropskog porekla se smatra da je 0.37 u plazmi i 0.44 u serumu^[7]^[8].

Molekularna biologija

Ovo je monomerni polipeptid, sa molekulskom težinom od aproksimativno 13 kDa. On je vezan za endotelijalne ćelije putem glikosaminoglikan bočnih lanaca proteoglikana. Njega prvenstveno izlučuju monociti, makrofage i dendritske ćelije. On je trombocit izvedeni faktor rasta induktivni gen. On se razlaže metaloproteinazom MMP-12.

Receptori na ćelijskoj površini koji vezuju CCL2 su CCR2 i CCR4.^[9]

Ovaj citokin deluje kao hemoatraktant za monocite i bazofile ali ne za neutrofile ili eozinofile. Brisanje N-terminalnih ostataka konvertuje ga iz aktivatora bazofila u eozinofil hemoatraktant. CCL2 uzrokuje degranulaciju bazofila i mast ćelija. Ovaj efekat je pojačan pre-tretmanom sa IL-3 i drugim citokinima.^[10]^[11] On menja monocitnu antitumorsku aktivnost, i on je esencijalan za formaciju granuloma.

Ovaj hemokin se može naći na mestu izvijanja zuba i degradacije kostiju. U kostima, CCL2 izražavaju osteoklasti i osteoblasti, i on je pod kontrolom nuklearnog faktora κB (NFκB). Za MCP-1 i RANTES je bilo pokazano da indukuju formaciju TRAP-pozitivnih, multinuklearnih ćelija iz M-CSF-tretiranih monocita u odsustvu RANKL, ali proizvode osteoklaste kojima nedostaje katepsin K ekspresija i resorptivni kapacitet. Predloženo je da CCL2 i RANTES dejstvuju kao autokrina petlja kod ljudske osteoklastne diferencijacije. ^[12]

Klinički značaj

CCL2 je bio impliciran u patogenezu bolesti karakterisane monocitnim infiltracijama, kao što su psorijaza, reumatoidni artritis i ateroskleroza.

Reference

↑ Carr MW, Roth SJ, Luther E, Rose SS, Springer TA (April 1994). „Monocyte chemoattractant protein 1 acts as a T-lymphocyte chemoattractant”. Proc. Natl. Acad. Sci. U.S.A. 91 (9): 3652–6. DOI:10.1073/pnas.91.9.3652. PMC 43639. PMID 8170963.
↑ Xu LL, Warren MK, Rose WL, Gong W, Wang JM (1996-01-09). „Human recombinant monocyte chemotactic protein and other C-C chemokines bind and induce directional migration of dendritic cells in vitro”. J. Leukoc. Biol. 60 (3): 365–71. PMID 8830793. ^{[mrtav link]}
↑ Mire-Sluis, Anthony R.; Thorpe, Robin, ur. (1998). Cytokines (Handbook of Immunopharmacology). Boston: Academic Press. ISBN 0-12-498340-5.
↑ Mehrabian M, Sparkes RS, Mohandas T, Fogelman AM, Lusis AJ (January 1991). „Localization of monocyte chemotactic protein-1 gene (SCYA2) to human chromosome 17q11.2-q21.1”. Genomics 9 (1): 200–3. DOI:10.1016/0888-7543(91)90239-B. PMID 2004761.
↑ Yoshimura T, Yuhki N, Moore SK, Appella E, Lerman MI, Leonard EJ (February 1989). „Human monocyte chemoattractant protein-1 (MCP-1). Full-length cDNA cloning, expression in mitogen-stimulated blood mononuclear leukocytes, and sequence similarity to mouse competence gene JE”. FEBS Lett. 244 (2): 487–93. DOI:10.1016/0014-5793(89)80590-3. PMID 2465924.
↑ Furutani Y, Nomura H, Notake M, Oyamada Y, Fukui T, Yamada M, Larsen CG, Oppenheim JJ, Matsushima K (February 1989). „Cloning and sequencing of the cDNA for human monocyte chemotactic and activating factor (MCAF)”. Biochem. Biophys. Res. Commun. 159 (1): 249–55. DOI:10.1016/0006-291X(89)92430-3. PMID 2923622.
↑ McDermott DH, Yang Q, Kathiresan S et al. (2005) CCL2 polymorphisms are associated with serum monocyte chemoattractant protein-1 levels and myocardial infarction in the Framingham Heart Study. Circulation 112(8):1113–1120
↑ Bielinski SJ, Pankow JS, Miller MB, et al (2007)Circulating MCP-1 levels shows linkage to chemokine receptor gene cluster on chromosome 3: the NHLBI family heart study follow-up examination. Genes Immun. 8(8):684–690
↑ Craig MJ, Loberg RD (December 2006). „CCL2 (Monocyte Chemoattractant Protein-1) in cancer bone metastases”. Cancer Metastasis Rev. 25 (4): 611–9. DOI:10.1007/s10555-006-9027-x. PMID 17160712.
↑ Conti P, Boucher W, Letourneau R, Feliciani C, Reale M, Barbacane RC, Vlagopoulos P, Bruneau G, Thibault J, Theoharides TC (November 1995). „Monocyte chemotactic protein-1 provokes mast cell aggregation and [3H5HT release”]. Immunology 86 (3): 434–40. PMC 1383948. PMID 8550082.
↑ Bischoff SC, Krieger M, Brunner T, Dahinden CA (May 1992). „Monocyte chemotactic protein 1 is a potent activator of human basophils”. J. Exp. Med. 175 (5): 1271–5. DOI:10.1084/jem.175.5.1271. PMC 2119199. PMID 1569397.
↑ Kim MS, Day CJ, Morrison NA (2005). „MCP-1 is induced by receptor activator of nuclear factorkappa}B ligand, promotes human osteoclast fusion, and rescues granulocyte macrophage colony-stimulating factor suppression of osteoclast formation”. J Biol Chem 280 (16): 16163-9. DOI:10.1074/jbc.M412713200. PMID 15722361.

Literatura

Yoshimura T, Leonard EJ (1992). „Human monocyte chemoattractant protein-1 (MCP-1).”. Adv. Exp. Med. Biol. 305: 47–56. PMID 1661560.
Wahl SM, Greenwell-Wild T, Hale-Donze H, et al. (2000). „Permissive factors for HIV-1 infection of macrophages.”. J. Leukoc. Biol. 68 (3): 303–10. PMID 10985244.
Sell H, Eckel J (2007). „Monocyte chemotactic protein-1 and its role in insulin resistance.”. Curr. Opin. Lipidol. 18 (3): 258–62. DOI:10.1097/MOL.0b013e3281338546. PMID 17495598.

Spoljašnje veze

CCL2 GeneCard

[pmid8170963-1] Carr MW, Roth SJ, Luther E, Rose SS, Springer TA (April 1994). „Monocyte chemoattractant protein 1 acts as a T-lymphocyte chemoattractant”. Proc. Natl. Acad. Sci. U.S.A. 91 (9): 3652–6. DOI:10.1073/pnas.91.9.3652. PMC 43639. PMID 8170963.

[pmid8830793-2] Xu LL, Warren MK, Rose WL, Gong W, Wang JM (1996-01-09). „Human recombinant monocyte chemotactic protein and other C-C chemokines bind and induce directional migration of dendritic cells in vitro”. J. Leukoc. Biol. 60 (3): 365–71. PMID 8830793. ^{[mrtav link]}

[3] Mire-Sluis, Anthony R.; Thorpe, Robin, ur. (1998). Cytokines (Handbook of Immunopharmacology). Boston: Academic Press. ISBN 0-12-498340-5.

[pmid2004761-4] Mehrabian M, Sparkes RS, Mohandas T, Fogelman AM, Lusis AJ (January 1991). „Localization of monocyte chemotactic protein-1 gene (SCYA2) to human chromosome 17q11.2-q21.1”. Genomics 9 (1): 200–3. DOI:10.1016/0888-7543(91)90239-B. PMID 2004761.

[pmid2465924-5] Yoshimura T, Yuhki N, Moore SK, Appella E, Lerman MI, Leonard EJ (February 1989). „Human monocyte chemoattractant protein-1 (MCP-1). Full-length cDNA cloning, expression in mitogen-stimulated blood mononuclear leukocytes, and sequence similarity to mouse competence gene JE”. FEBS Lett. 244 (2): 487–93. DOI:10.1016/0014-5793(89)80590-3. PMID 2465924.

[pmid2923622-6] Furutani Y, Nomura H, Notake M, Oyamada Y, Fukui T, Yamada M, Larsen CG, Oppenheim JJ, Matsushima K (February 1989). „Cloning and sequencing of the cDNA for human monocyte chemotactic and activating factor (MCAF)”. Biochem. Biophys. Res. Commun. 159 (1): 249–55. DOI:10.1016/0006-291X(89)92430-3. PMID 2923622.

[McDermott2005-7] McDermott DH, Yang Q, Kathiresan S et al. (2005) CCL2 polymorphisms are associated with serum monocyte chemoattractant protein-1 levels and myocardial infarction in the Framingham Heart Study. Circulation 112(8):1113–1120

[Bielinski2007-8] Bielinski SJ, Pankow JS, Miller MB, et al (2007)Circulating MCP-1 levels shows linkage to chemokine receptor gene cluster on chromosome 3: the NHLBI family heart study follow-up examination. Genes Immun. 8(8):684–690

[pmid17160712-9] Craig MJ, Loberg RD (December 2006). „CCL2 (Monocyte Chemoattractant Protein-1) in cancer bone metastases”. Cancer Metastasis Rev. 25 (4): 611–9. DOI:10.1007/s10555-006-9027-x. PMID 17160712.

[pmid8550082-10] Conti P, Boucher W, Letourneau R, Feliciani C, Reale M, Barbacane RC, Vlagopoulos P, Bruneau G, Thibault J, Theoharides TC (November 1995). „Monocyte chemotactic protein-1 provokes mast cell aggregation and [3H5HT release”]. Immunology 86 (3): 434–40. PMC 1383948. PMID 8550082.

[pmid1569397-11] Bischoff SC, Krieger M, Brunner T, Dahinden CA (May 1992). „Monocyte chemotactic protein 1 is a potent activator of human basophils”. J. Exp. Med. 175 (5): 1271–5. DOI:10.1084/jem.175.5.1271. PMC 2119199. PMID 1569397.

[Kim-12] Kim MS, Day CJ, Morrison NA (2005). „MCP-1 is induced by receptor activator of nuclear factorkappa}B ligand, promotes human osteoclast fusion, and rescues granulocyte macrophage colony-stimulating factor suppression of osteoclast formation”. J Biol Chem 280 (16): 16163-9. DOI:10.1074/jbc.M412713200. PMID 15722361.

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