“GNLY”的意思、由来-开放百科全书

Granulysin, also known as GNLY, is a protein which in humans is encoded by the GNLY gene.^[1] It is also known as NK-lysin (NKL) after NK cells;^[1] the cattle ortholog is sometimes referred to as Bo-lysin.

Function

Granulysin is a protein present in cytotoxic granules of cytotoxic T cells and natural killer cells. Granulysin is a member of the saposin-like protein (SAPLIP) family and is released from cytotoxic T cells upon antigen stimulation. Granulysin has antimicrobial activity against M. tuberculosis and other organisms. Granulysin is alternatively spliced, resulting in the NKG5 and 519 transcripts.^[2]

Granulysin is a cytolytic and proinflammatory molecule first identified by a screen for genes expressed “late” (3–5 days) after activation of human peripheral blood mononuclear cells.^[3] Granulysin is present in cytolytic granules of cytotoxic T lymphocytes (CTL) and natural killer (NK) cells. Granulysin is made as a 15 kD molecule, and a portion of it is cleaved at both the amino and carboxy termini into a 9 kD form. The 9 kD form is released by receptor-mediated granule exocytosis while the 15 kD form is constitutively secreted. Recombinant 9 kD granulysin is broadly cytolytic against tumors and microbes, including gram positive and gram negative bacteria, fungi/yeast and parasites.^[4] 9kD granulysin is also a chemoattractant for T lymphocytes, monocytes, and other inflammatory cells and activates the expression of a number of cytokines, including RANTES, MCP-1, MCP-3, MIP-1α, IL-10, IL-1, IL-6 and IFNα.^[5] Granulysin has been implicated in a myriad of diseases including infection, cancer, transplantation, autoimmunity, skin and reproductive maladies.^[6]

Evolution

GNLY orthologs have been identified in multiple species, including pigs, chicken, and cattle. Cattle has multiple copies of the gene with functional diversification.^[7]

Mice do not have a granulysin homolog, but transgenic mice expressing human granulysin have been engineered.^[8]

References

1. ^{{cite journal | vauthors = Andersson M, Gunne H, Agerberth B, Boman A, Bergman T, Sillard R, Jörnvall H, Mutt V, Olsson B, Wigzell H | title = NK-lysin, a novel effector peptide of cytotoxic T and NK cells. Structure and cDNA cloning of the porcine form, induction by interleukin 2, antibacterial and antitumour activity | journal = The EMBO Journal | volume = 14 | issue = 8 | pages = 1615–25 | date = April 1995 | pmid = 7737114 | pmc = 398254 }}
2. ^¹{{cite web | title = Entrez Gene: GNLY granulysin| url = https://www.ncbi.nlm.nih.gov/sites/entrez?Db=gene&Cmd=ShowDetailView&TermToSearch=10578| access-date = }}
3. ^{{cite journal | vauthors = Jongstra J, Schall TJ, Dyer BJ, Clayberger C, Jorgensen J, Davis MM, Krensky AM | title = The isolation and sequence of a novel gene from a human functional T cell line | journal = The Journal of Experimental Medicine | volume = 165 | issue = 3 | pages = 601–14 | date = March 1987 | pmid = 2434598 | pmc = 2188281 | doi = 10.1084/jem.165.3.601 }}
4. ^{{cite journal | vauthors = Stenger S, Hanson DA, Teitelbaum R, Dewan P, Niazi KR, Froelich CJ, Ganz T, Thoma-Uszynski S, Melián A, Bogdan C, Porcelli SA, Bloom BR, Krensky AM, Modlin RL | title = An antimicrobial activity of cytolytic T cells mediated by granulysin | journal = Science | volume = 282 | issue = 5386 | pages = 121–5 | date = October 1998 | pmid = 9756476 | doi = 10.1126/science.282.5386.121 }}
5. ^{{cite journal | vauthors = Deng A, Chen S, Li Q, Lyu SC, Clayberger C, Krensky AM | title = Granulysin, a cytolytic molecule, is also a chemoattractant and proinflammatory activator | journal = Journal of Immunology | volume = 174 | issue = 9 | pages = 5243–8 | date = May 2005 | pmid = 15843520 | doi = 10.4049/jimmunol.174.9.5243 | url = http://www.jimmunol.org/cgi/content/abstract/174/9/5243 }}
6. ^{{cite journal | vauthors = Krensky AM, Clayberger C | title = Biology and clinical relevance of granulysin | journal = Tissue Antigens | volume = 73 | issue = 3 | pages = 193–8 | date = March 2009 | pmid = 19254247 | pmc = 2679253 | doi = 10.1111/j.1399-0039.2008.01218.x }}
7. ^{{cite journal | vauthors = Chen J, Huddleston J, Buckley RM, Malig M, Lawhon SD, Skow LC, Lee MO, Eichler EE, Andersson L, Womack JE | title = Bovine NK-lysin: Copy number variation and functional diversification | journal = Proceedings of the National Academy of Sciences of the United States of America | volume = 112 | issue = 52 | pages = E7223-9 | date = December 2015 | pmid = 26668394 | pmc = 4702975 | doi = 10.1073/pnas.1519374113 }}
8. ^{{cite journal | vauthors = Huang LP, Lyu SC, Clayberger C, Krensky AM | title = Granulysin-mediated tumor rejection in transgenic mice | journal = Journal of Immunology | volume = 178 | issue = 1 | pages = 77–84 | date = January 2007 | pmid = 17182542 | pmc = 2664664 | doi = 10.4049/jimmunol.178.1.77 | url = http://www.jimmunol.org/cgi/content/full/178/1/77 }}

Function

Evolution

References

Further reading