GNLY
Granulysin, also known as GNLY, is a protein which in humans is encoded by the GNLY gene.[1]
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.[1]
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.[2] 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.[3] 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.[4] Mice do not have a granulysin homolog, but transgenic mice expressing human granulysin have been engineered.[5] Granulysin has been implicated in a myriad of diseases including infection, cancer, transplantation, autoimmunity, skin and reproductive maladies.[6]
References
- ^ a b "Entrez Gene: GNLY granulysin". http://www.ncbi.nlm.nih.gov/sites/entrez?Db=gene&Cmd=ShowDetailView&TermToSearch=10578.
- ^ Jongstra J, Schall TJ, Dyer BJ, Clayberger C, Jorgensen J, Davis MM, Krensky AM (March 1987). "The isolation and sequence of a novel gene from a human functional T cell line". J. Exp. Med. 165 (3): 601–14. doi:10.1084/jem.165.3.601. PMC 2188281. PMID 2434598. http://www.pubmedcentral.nih.gov/articlerender.fcgi?tool=pmcentrez&artid=2188281.
- ^ 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 (October 1998). "An antimicrobial activity of cytolytic T cells mediated by granulysin". Science 282 (5386): 121–5. doi:10.1126/science.282.5386.121. PMID 9756476.
- ^ Deng A, Chen S, Li Q, Lyu SC, Clayberger C, Krensky AM (May 2005). "Granulysin, a cytolytic molecule, is also a chemoattractant and proinflammatory activator". J. Immunol. 174 (9): 5243–8. PMID 15843520. http://www.jimmunol.org/cgi/content/abstract/174/9/5243.
- ^ Huang LP, Lyu SC, Clayberger C, Krensky AM (January 2007). "Granulysin-Mediated Tumor Rejection in Transgenic Mice". J. Immunol. 178 (1): 77–84. PMC 2664664. PMID 17182542. http://www.jimmunol.org/cgi/content/full/178/1/77.
- ^ Krensky AM, Clayberger C (March 2009). "Biology and clinical relevance of granulysin". Tissue Antigens 73 (3): 193–8. doi:10.1111/j.1399-0039.2008.01218.x. PMC 2679253. PMID 19254247. http://www.pubmedcentral.nih.gov/articlerender.fcgi?tool=pmcentrez&artid=2679253.
Further reading
- Peña SV, Krensky AM (1997). "Granulysin, a new human cytolytic granule-associated protein with possible involvement in cell-mediated cytotoxicity". Semin. Immunol. 9 (2): 117–25. doi:10.1006/smim.1997.0061. PMID 9194222.
- Krensky AM (2000). "Granulysin: a novel antimicrobial peptide of cytolytic T lymphocytes and natural killer cells". Biochem. Pharmacol. 59 (4): 317–20. doi:10.1016/S0006-2952(99)00177-X. PMID 10644038.
- Donlon TA, Krensky AM, Clayberger C (1990). "Localization of the human T lymphocyte activation gene 519 (D2S69E) to chromosome 2p12----q11". Cytogenet. Cell Genet. 53 (4): 230–1. doi:10.1159/000132938. PMID 2209093.
- Yabe T, McSherry C, Bach FH, Houchins JP (1990). "A cDNA clone expressed in natural killer and T cells that likely encodes a secreted protein". J. Exp. Med. 172 (4): 1159–63. doi:10.1084/jem.172.4.1159. PMC 2188624. PMID 2212946. http://www.pubmedcentral.nih.gov/articlerender.fcgi?tool=pmcentrez&artid=2188624.
- Jongstra J, Schall TJ, Dyer BJ, et al. (1987). "The isolation and sequence of a novel gene from a human functional T cell line". J. Exp. Med. 165 (3): 601–14. doi:10.1084/jem.165.3.601. PMC 2188281. PMID 2434598. http://www.pubmedcentral.nih.gov/articlerender.fcgi?tool=pmcentrez&artid=2188281.
- Houchins JP, Kricek F, Chujor CS, et al. (1993). "Genomic structure of NKG5, a human NK and T cell-specific activation gene". Immunogenetics 37 (2): 102–7. doi:10.1007/BF00216832. PMID 8423048.
- Peña SV, Hanson DA, Carr BA, et al. (1997). "Processing, subcellular localization, and function of 519 (granulysin), a human late T cell activation molecule with homology to small, lytic, granule proteins". J. Immunol. 158 (6): 2680–8. PMID 9058801.
- Stenger S, Hanson DA, Teitelbaum R, et al. (1998). "An antimicrobial activity of cytolytic T cells mediated by granulysin". Science 282 (5386): 121–5. doi:10.1126/science.282.5386.121. PMID 9756476.
- Hanson DA, Kaspar AA, Poulain FR, Krensky AM (1999). "Biosynthesis of granulysin, a novel cytolytic molecule". Mol. Immunol. 36 (7): 413–22. doi:10.1016/S0161-5890(99)00063-2. PMID 10449094.
- Kaspar AA, Okada S, Kumar J, et al. (2001). "A distinct pathway of cell-mediated apoptosis initiated by granulysin". J. Immunol. 167 (1): 350–6. PMID 11418670.
- Kitamura N, Koshiba M, Horie O, Ryo R (2002). "Expression of granulysin mRNA in the human megakaryoblastic leukemia cell line CMK". Acta Haematol. 108 (1): 13–8. doi:10.1159/000063061. PMID 12145461.
- Ma LL, Spurrell JC, Wang JF, et al. (2003). "CD8 T cell-mediated killing of Cryptococcus neoformans requires granulysin and is dependent on CD4 T cells and IL-15". J. Immunol. 169 (10): 5787–95. PMID 12421959.
- Strausberg RL, Feingold EA, Grouse LH, et al. (2003). "Generation and initial analysis of more than 15,000 full-length human and mouse cDNA sequences". Proc. Natl. Acad. Sci. U.S.A. 99 (26): 16899–903. doi:10.1073/pnas.242603899. PMC 139241. PMID 12477932. http://www.pubmedcentral.nih.gov/articlerender.fcgi?tool=pmcentrez&artid=139241.
- Ericson KG, Fadeel B, Andersson M, et al. (2003). "Sequence analysis of the granulysin and granzyme B genes in familial hemophagocytic lymphohistiocytosis". Hum. Genet. 112 (1): 98–9. doi:10.1007/s00439-002-0841-0. PMID 12483306.
- Anderson DH, Sawaya MR, Cascio D, et al. (2003). "Granulysin crystal structure and a structure-derived lytic mechanism". J. Mol. Biol. 325 (2): 355–65. doi:10.1016/S0022-2836(02)01234-2. PMID 12488100.
- Gansert JL, Kiessler V, Engele M, et al. (2003). "Human NKT cells express granulysin and exhibit antimycobacterial activity". J. Immunol. 170 (6): 3154–61. PMID 12626573.
- Ogawa K, Takamori Y, Suzuki K, et al. (2003). "Granulysin in human serum as a marker of cell-mediated immunity". Eur. J. Immunol. 33 (7): 1925–33. doi:10.1002/eji.200323977. PMID 12884856.
- Kotsch K, Mashreghi MF, Bold G, et al. (2004). "Enhanced granulysin mRNA expression in urinary sediment in early and delayed acute renal allograft rejection". Transplantation 77 (12): 1866–75. doi:10.1097/01.TP.0000131157.19937.3F. PMID 15223905.
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1l9l: GRANULYSIN FROM HUMAN CYTOLYTIC T LYMPHOCYTES
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