Keratin 18 Explained

Keratin 18 is a type I cytokeratin. It is, together with its filament partner keratin 8, perhaps the most commonly found products of the intermediate filament gene family. They are expressed in single layer epithelial tissues of the body. Mutations in this gene have been linked to cryptogenic cirrhosis. Two transcript variants encoding the same protein have been found for this gene.^[1]

Keratin 18 is often used together with keratin 8 and keratin 19 to differentiate cells of epithelial origin from hematopoietic cells in tests that enumerate circulating tumor cells in blood.^[2]

Interactions

Keratin 18 has been shown to interact with Collagen, type XVII, alpha 1,^[3] DNAJB6,^[4] Pinin^[5] and TRADD.^[6]

Further reading

• Omary MB, Baxter GT, Chou CF, etal . PKC epsilon-related kinase associates with and phosphorylates cytokeratin 8 and 18 . J. Cell Biol. . 117 . 3 . 583–93 . 1992 . 1374067 . 10.1083/jcb.117.3.583 . 2289443.
• Waseem A, Gough AC, Spurr NK, Lane EB . Localization of the gene for human simple epithelial keratin 18 to chromosome 12 using polymerase chain reaction . Genomics . 7 . 2 . 188–94 . 1990 . 1693358 . 10.1016/0888-7543(90)90540-B.
• Heath P, Elvin P, Jenner D, etal . Localisation of a cDNA clone for human cytokeratin 18 to chromosome 17p11-p12 by in situ hybridisation . Hum. Genet. . 85 . 6 . 669–70 . 1990 . 1699878 . 10.1007/BF00193596. 19296094 .
• Waseem A, Alexander CM, Steel JB, Lane EB . Embryonic simple epithelial keratins 8 and 18: chromosomal location emphasizes difference from other keratin pairs . New Biol. . 2 . 5 . 464–78 . 1991 . 1705144 .
• Romano V, Hatzfeld M, Magin TM, etal . Cytokeratin expression in simple epithelia. I. Identification of mRNA coding for human cytokeratin no. 18 by a cDNA clone . Differentiation . 30 . 3 . 244–53 . 1986 . 2422083 . 10.1111/j.1432-0436.1986.tb00787.x.
• Oshima RG, Millán JL, Ceceña G . Comparison of mouse and human keratin 18: a component of intermediate filaments expressed prior to implantation . Differentiation . 33 . 1 . 61–8 . 1987 . 2434380 . 10.1111/j.1432-0436.1987.tb01542.x.
• Leube RE, Bosch FX, Romano V, etal . Cytokeratin expression in simple epithelia. III. Detection of mRNAs encoding human cytokeratins nos. 8 and 18 in normal and tumor cells by hybridization with cDNA sequences in vitro and in situ . Differentiation . 33 . 1 . 69–85 . 1987 . 2434381 . 10.1111/j.1432-0436.1986.tb00412.x.
• Kulesh DA, Oshima RG . Cloning of the human keratin 18 gene and its expression in nonepithelial mouse cells . Mol. Cell. Biol. . 8 . 4 . 1540–50 . 1988 . 2454392 . 10.1128/MCB.8.4.1540. 363314 .
• Sémat A, Vasseur M, Maillet L, etal . Sequence analysis of murine cytokeratin endo A (no. 8) cDNA. Evidence for mRNA species initiated upstream of the normal 5' end in PCC4 cells . Differentiation . 37 . 1 . 40–6 . 1988 . 2454862 . 10.1111/j.1432-0436.1988.tb00794.x.
• Kulesh DA, Oshima RG . Complete structure of the gene for human keratin 18 . Genomics . 4 . 3 . 339–47 . 1989 . 2469635 . 10.1016/0888-7543(89)90340-6.
• Ku NO, Omary MB . Identification of the major physiologic phosphorylation site of human keratin 18: potential kinases and a role in filament reorganization . J. Cell Biol. . 127 . 1 . 161–71 . 1994 . 7523419 . 10.1083/jcb.127.1.161 . 2120194.
• Liao J, Lowthert LA, Ghori N, Omary MB . The 70-kDa heat shock proteins associate with glandular intermediate filaments in an ATP-dependent manner . J. Biol. Chem. . 270 . 2 . 915–22 . 1995 . 7529764 . 10.1074/jbc.270.2.915 . free .
• Yoon SJ, LeBlanc-Straceski J, Ward D, etal . Organization of the human keratin type II gene cluster at 12q13 . Genomics . 24 . 3 . 502–8 . 1995 . 7536183 . 10.1006/geno.1994.1659 . free .
• Ku NO, Omary MB . Identification and mutational analysis of the glycosylation sites of human keratin 18 . J. Biol. Chem. . 270 . 20 . 11820–7 . 1995 . 7538124 . 10.1074/jbc.270.20.11820 . free .
• Neumaier M, Gerhard M, Wagener C . Diagnosis of micrometastases by the amplification of tissue-specific genes . Gene . 159 . 1 . 43–7 . 1995 . 7541767 . 10.1016/0378-1119(94)00522-T.
• Maruyama K, Sugano S . Oligo-capping: a simple method to replace the cap structure of eukaryotic mRNAs with oligoribonucleotides . Gene . 138 . 1–2 . 171–4 . 1994 . 8125298 . 10.1016/0378-1119(94)90802-8 .
• Liao J, Lowthert LA, Ku NO, etal . Dynamics of human keratin 18 phosphorylation: polarized distribution of phosphorylated keratins in simple epithelial tissues . J. Cell Biol. . 131 . 5 . 1291–301 . 1996 . 8522590 . 10.1083/jcb.131.5.1291 . 2120635 .
• Ku NO, Wright TL, Terrault NA, etal . Mutation of human keratin 18 in association with cryptogenic cirrhosis . J. Clin. Invest. . 99 . 1 . 19–23 . 1997 . 9011570 . 10.1172/JCI119127 . 507762.
• Ji H, Reid GE, Moritz RL, etal . A two-dimensional gel database of human colon carcinoma proteins . Electrophoresis . 18 . 3–4 . 605–13 . 1997 . 9150948 . 10.1002/elps.1150180344 . 25454450 .

Notes and References

1. Web site: Entrez Gene: KRT18 keratin 18.
2. W. Jeffrey Allard . Jeri Matera . M. Craig Miller . Tumor Cells Circulate in the Peripheral Blood of All Major Carcinomas but not in Healthy Subjects or Patients With Nonmalignant Diseases . Clinical Cancer Research . 10 . 6897–6904 . October 2004 . 10.1158/1078-0432.CCR-04-0378 . 15501967 . 20. etal. free .
3. Aho . S . Uitto J . March 1999 . 180-kD bullous pemphigoid antigen/type XVII collagen: tissue-specific expression and molecular interactions with keratin 18 . J. Cell. Biochem. . 72 . 3 . 356–67 . 0730-2312. 10022517 . 10.1002/(SICI)1097-4644(19990301)72:3<356::AID-JCB5>3.0.CO;2-M . 30404639 .
4. Izawa . I . Nishizawa M . Ohtakara K . Ohtsuka K . Inada H . Inagaki M . November 2000 . Identification of Mrj, a DnaJ/Hsp40 family protein, as a keratin 8/18 filament regulatory protein . J. Biol. Chem. . 275 . 44 . 34521–7 . 0021-9258. 10954706 . 10.1074/jbc.M003492200 . free .
5. Shi . J . Sugrue S P . May 2000 . Dissection of protein linkage between keratins and pinin, a protein with dual location at desmosome-intermediate filament complex and in the nucleus . J. Biol. Chem. . 275 . 20 . 14910–5 . 0021-9258. 10809736 . 10.1074/jbc.275.20.14910 . free.
6. Inada . H . Izawa I . Nishizawa M . Fujita E . Kiyono T . Takahashi T . Momoi T . Inagaki M . October 2001 . Keratin attenuates tumor necrosis factor-induced cytotoxicity through association with TRADD . J. Cell Biol. . 155 . 3 . 415–26 . 0021-9525. 11684708 . 10.1083/jcb.200103078 . 2150850 .