PMCCPMCCPMCC

Search tips
Search criteria 

Advanced

 
Logo of jcellbiolHomeThe Rockefeller University PressEditorsContactInstructions for AuthorsThis issue
 
J Cell Biol. 1984 April 1; 98(4): 1388–1396.
PMCID: PMC2113226

Classification of epidermal keratins according to their immunoreactivity, isoelectric point, and mode of expression

Abstract

Human epidermal keratinocytes express under various growth conditions a total of at least nine keratins that can be divided into two subfamilies. Subfamily A comprises 40-, 46-, 48-, 50-/50'-, and 56.5- kilodalton (kd) keratins which are relatively acidic (pI less than 5.5) and, with the exception of 46-kd keratin, are recognized by AE1 monoclonal antibody. Subfamily B comprises 52-, 56-, 58-, and 65-67-kd keratins which are relatively basic (pI greater than 6) and are recognized by AE3 monoclonal antibody. Within each keratin subfamily, there is a constant member (50-/50'- and 58-kd keratins of the subfamilies A and B, respectively) that is always expressed. The other seven keratins of both subfamilies are variable members whose expression depends upon the cellular differentiated state, which is in turn modulated by the growth environment. The 56.5-kd keratin (subfamily A) and the 65-67-kd keratins (subfamily B) are coordinately expressed during keratinization. In contrast, the 40-, 46-, and 48-kd keratins (subfamily A) and the 52- and 56-kd keratins (subfamily B) are characteristic of cultured epidermal cells forming nonkeratinized colonies. These results demonstrate that human epidermal keratins can be classified according to their reactivity with monoclonal antikeratin antibodies, isoelectric point, and mode of expression. The classification of keratins into various subgroups may have important implications for the mechanisms of epidermal differentiation, the evolution of keratin heterogeneity, and the use of keratin markers for tumor diagnosis.

Full Text

The Full Text of this article is available as a PDF (1.5M).

Selected References

These references are in PubMed. This may not be the complete list of references from this article.
  • Baden HP, Kubilus J, Argyris TS. Modification of polypeptide composition in keratinocyte fibrous protein. J Invest Dermatol. 1980 Nov;75(5):383–387. [PubMed]
  • Baden HP, Lee LD. Fibrous protein of human epidermis. J Invest Dermatol. 1978 Aug;71(2):148–151. [PubMed]
  • Banks-Schlegel S, Green H. Formation of epidermis by serially cultivated human epidermal cells transplanted as an epithelium to athymic mice. Transplantation. 1980 Apr;29(4):308–313. [PubMed]
  • Bissell MJ. The differentiated state of normal and malignant cells or how to define a "normal" cell in culture. Int Rev Cytol. 1981;70:27–100. [PubMed]
  • Bladon PT, Bowden PE, Cunliffe WJ, Wood EJ. Prekeratin biosynthesis in human scalp epidermis. Biochem J. 1982 Oct 15;208(1):179–187. [PubMed]
  • Bowden PE, Cunliffe WJ. Modification of human prekeratin during epidermal differentiation. Biochem J. 1981 Oct 1;199(1):145–154. [PubMed]
  • Denk H, Krepler R, Lackinger E, Artlieb U, Franke WW. Biochemical and immunocytochemical analysis of the intermediate filament cytoskeleton in human hepatocellular carcinomas and in hepatic neoplastic nodules of mice. Lab Invest. 1982 Jun;46(6):584–596. [PubMed]
  • Doran TI, Vidrich A, Sun TT. Intrinsic and extrinsic regulation of the differentiation of skin, corneal and esophageal epithelial cells. Cell. 1980 Nov;22(1 Pt 1):17–25. [PubMed]
  • Franke WW, Denk H, Kalt R, Schmid E. Biochemical and immunological identification of cytokeratin proteins present in hepatocytes of mammalian liver tissue. Exp Cell Res. 1981 Feb;131(2):299–318. [PubMed]
  • Franke WW, Schiller DL, Moll R, Winter S, Schmid E, Engelbrecht I, Denk H, Krepler R, Platzer B. Diversity of cytokeratins. Differentiation specific expression of cytokeratin polypeptides in epithelial cells and tissues. J Mol Biol. 1981 Dec 25;153(4):933–959. [PubMed]
  • Franke WW, Schmid E, Osborn M, Weber K. Different intermediate-sized filaments distinguished by immunofluorescence microscopy. Proc Natl Acad Sci U S A. 1978 Oct;75(10):5034–5038. [PubMed]
  • Franke WW, Weber K, Osborn M, Schmid E, Freudenstein C. Antibody to prekeratin. Decoration of tonofilament like arrays in various cells of epithelial character. Exp Cell Res. 1978 Oct 15;116(2):429–445. [PubMed]
  • Franke WW, Winter S, Grund C, Schmid E, Schiller DL, Jarasch ED. Isolation and characterization of desmosome-associated tonofilaments from rat intestinal brush border. J Cell Biol. 1981 Jul;90(1):116–127. [PMC free article] [PubMed]
  • Fuchs EV, Coppock SM, Green H, Cleveland DW. Two distinct classes of keratin genes and their evolutionary significance. Cell. 1981 Nov;27(1 Pt 2):75–84. [PubMed]
  • Fuchs E, Green H. The expression of keratin genes in epidermis and cultured epidermal cells. Cell. 1978 Nov;15(3):887–897. [PubMed]
  • Fuchs E, Green H. Changes in keratin gene expression during terminal differentiation of the keratinocyte. Cell. 1980 Apr;19(4):1033–1042. [PubMed]
  • Fuchs E, Green H. Regulation of terminal differentiation of cultured human keratinocytes by vitamin A. Cell. 1981 Sep;25(3):617–625. [PubMed]
  • Gigi O, Geiger B, Eshhar Z, Moll R, Schmid E, Winter S, Schiller DL, Franke WW. Detection of a cytokeratin determinant common to diverse epithelial cells by a broadly cross-reacting monoclonal antibody. EMBO J. 1982;1(11):1429–1437. [PubMed]
  • Gilmartin ME, Culbertson VB, Freedberg IM. Phosphorylation of epidermal keratins. J Invest Dermatol. 1980 Sep;75(3):211–216. [PubMed]
  • Gipson IK, Anderson RA. Comparison of 10 nm filaments from three bovine tissues. Exp Cell Res. 1980 Aug;128(2):395–406. [PubMed]
  • Green H, Fuchs E, Watt F. Differentiated structural components of the keratinocyte. Cold Spring Harb Symp Quant Biol. 1982;46(Pt 1):293–301. [PubMed]
  • Hanukoglu I, Fuchs E. The cDNA sequence of a Type II cytoskeletal keratin reveals constant and variable structural domains among keratins. Cell. 1983 Jul;33(3):915–924. [PubMed]
  • Kim KH, Rheinwald JG, Fuchs EV. Tissue specificity of epithelial keratins: differential expression of mRNAs from two multigene families. Mol Cell Biol. 1983 Apr;3(4):495–502. [PMC free article] [PubMed]
  • Köhler G, Milstein C. Continuous cultures of fused cells secreting antibody of predefined specificity. Nature. 1975 Aug 7;256(5517):495–497. [PubMed]
  • Kubilus J, Baden HP, McGilvray N. Filamentous protein of basal cell epithelioma: characteristics in vivo and in vitro. J Natl Cancer Inst. 1980 Nov;65(5):869–875. [PubMed]
  • Kubilus J, MacDonald MJ, Baden HP. Epidermal proteins of cultured human and bovine keratinocytes. Biochim Biophys Acta. 1979 Jun 19;578(2):484–492. [PubMed]
  • Lavker RM, Sun TT. Rapid modulation of keratinocyte differentiation by the external environment. J Invest Dermatol. 1983 Apr;80(4):228–237. [PubMed]
  • Lavker RM, Sun TT. Epidermal stem cells. J Invest Dermatol. 1983 Jul;81(1 Suppl):121s–127s. [PubMed]
  • Lazarides E. Intermediate filaments: a chemically heterogeneous, developmentally regulated class of proteins. Annu Rev Biochem. 1982;51:219–250. [PubMed]
  • Lee LD, Baden HP. Organisation of the polypeptide chains in mammalian keratin. Nature. 1976 Nov 25;264(5584):377–379. [PubMed]
  • Moll R, Franke WW, Schiller DL, Geiger B, Krepler R. The catalog of human cytokeratins: patterns of expression in normal epithelia, tumors and cultured cells. Cell. 1982 Nov;31(1):11–24. [PubMed]
  • Moll R, Franke WW, Volc-Platzer B, Krepler R. Different keratin polypeptides in epidermis and other epithelia of human skin: a specific cytokeratin of molecular weight 46,000 in epithelia of the pilosebaceous tract and basal cell epitheliomas. J Cell Biol. 1982 Oct;95(1):285–295. [PMC free article] [PubMed]
  • Moll R, Krepler R, Franke WW. Complex cytokeratin polypeptide patterns observed in certain human carcinomas. Differentiation. 1983;23(3):256–269. [PubMed]
  • Moll R, Moll I, Wiest W. Changes in the pattern of cytokeratin polypeptides in epidermis and hair follicles during skin development in human fetuses. Differentiation. 1982;23(2):170–178. [PubMed]
  • Nelson WG, Sun TT. The 50- and 58-kdalton keratin classes as molecular markers for stratified squamous epithelia: cell culture studies. J Cell Biol. 1983 Jul;97(1):244–251. [PMC free article] [PubMed]
  • O'Farrell PH. High resolution two-dimensional electrophoresis of proteins. J Biol Chem. 1975 May 25;250(10):4007–4021. [PMC free article] [PubMed]
  • O'Farrell PZ, Goodman HM, O'Farrell PH. High resolution two-dimensional electrophoresis of basic as well as acidic proteins. Cell. 1977 Dec;12(4):1133–1141. [PubMed]
  • Rheinwald JG, Green H. Serial cultivation of strains of human epidermal keratinocytes: the formation of keratinizing colonies from single cells. Cell. 1975 Nov;6(3):331–343. [PubMed]
  • Rheinwald JG, Green H. Epidermal growth factor and the multiplication of cultured human epidermal keratinocytes. Nature. 1977 Feb 3;265(5593):421–424. [PubMed]
  • Roop DR, Hawley-Nelson P, Cheng CK, Yuspa SH. Keratin gene expression in mouse epidermis and cultured epidermal cells. Proc Natl Acad Sci U S A. 1983 Feb;80(3):716–720. [PubMed]
  • Schiller DL, Franke WW, Geiger B. A subfamily of relatively large and basic cytokeratin polypeptides as defined by peptide mapping is represented by one or several polypeptides in epithelial cells. EMBO J. 1982;1(6):761–769. [PubMed]
  • Skerrow D, Skerrow CJ. Tonofilament differentiation in human epidermis, isolation and polypeptide chain composition of keratinocyte subpopulations. Exp Cell Res. 1983 Jan;143(1):27–35. [PubMed]
  • Steinert PM, Idler WW. Postsynthetic modifications of mammalian epidermal alpha-keratin. Biochemistry. 1979 Dec 11;18(25):5664–5669. [PubMed]
  • Steinert PM, Idler WW, Zimmerman SB. Self-assembly of bovine epidermal keratin filaments in vitro. J Mol Biol. 1976 Dec 15;108(3):547–567. [PubMed]
  • Steinert P, Yuspa SH. Biochemical evidence for keratinization by mouse epidermal cells in culture. Science. 1978 Jun 30;200(4349):1491–1493. [PubMed]
  • Sun TT, Eichner R, Nelson WG, Vidrich A, Woodcock-Mitchell J. Keratin expression during normal epidermal differentiation. Curr Probl Dermatol. 1983;11:277–291. [PubMed]
  • Sun TT, Eichner R, Nelson WG, Tseng SC, Weiss RA, Jarvinen M, Woodcock-Mitchell J. Keratin classes: molecular markers for different types of epithelial differentiation. J Invest Dermatol. 1983 Jul;81(1 Suppl):109s–115s. [PubMed]
  • Sun TT, Green H. Differentiation of the epidermal keratinocyte in cell culture: formation of the cornified envelope. Cell. 1976 Dec;9(4 Pt 1):511–521. [PubMed]
  • Sun TT, Green H. Cultured epithelial cells of cornea, conjunctiva and skin: absence of marked intrinsic divergence of their differentiated states. Nature. 1977 Oct 6;269(5628):489–493. [PubMed]
  • Sun TT, Green H. Keratin filaments of cultured human epidermal cells. Formation of intermolecular disulfide bonds during terminal differentiation. J Biol Chem. 1978 Mar 25;253(6):2053–2060. [PubMed]
  • Sun TT, Green H. Immunofluorescent staining of keratin fibers in cultured cells. Cell. 1978 Jul;14(3):469–476. [PubMed]
  • Sun TT, Shih C, Green H. Keratin cytoskeletons in epithelial cells of internal organs. Proc Natl Acad Sci U S A. 1979 Jun;76(6):2813–2817. [PubMed]
  • Taichman LB, Prokop CA. Synthesis of keratin proteins during maturation of cultured human keratinocytes. J Invest Dermatol. 1982 Jun;78(6):464–467. [PubMed]
  • Towbin H, Staehelin T, Gordon J. Electrophoretic transfer of proteins from polyacrylamide gels to nitrocellulose sheets: procedure and some applications. Proc Natl Acad Sci U S A. 1979 Sep;76(9):4350–4354. [PubMed]
  • Tseng SC, Jarvinen MJ, Nelson WG, Huang JW, Woodcock-Mitchell J, Sun TT. Correlation of specific keratins with different types of epithelial differentiation: monoclonal antibody studies. Cell. 1982 Sep;30(2):361–372. [PubMed]
  • Viac J, Staquet MJ, Thivolet J, Goujon C. Experimental production of antibodies against stratum corneum keratin polypeptides. Arch Dermatol Res. 1980;267(2):179–188. [PubMed]
  • Weiss RA, Eichner R, Sun TT. Monoclonal antibody analysis of keratin expression in epidermal diseases: a 48- and 56-kdalton keratin as molecular markers for hyperproliferative keratinocytes. J Cell Biol. 1984 Apr;98(4):1397–1406. [PMC free article] [PubMed]
  • Weiss RA, Guillet GY, Freedberg IM, Farmer ER, Small EA, Weiss MM, Sun TT. The use of monoclonal antibody to keratin in human epidermal disease: alterations in immunohistochemical staining pattern. J Invest Dermatol. 1983 Sep;81(3):224–230. [PubMed]
  • Woodcock-Mitchell J, Eichner R, Nelson WG, Sun TT. Immunolocalization of keratin polypeptides in human epidermis using monoclonal antibodies. J Cell Biol. 1982 Nov;95(2 Pt 1):580–588. [PMC free article] [PubMed]
  • Wu YJ, Parker LM, Binder NE, Beckett MA, Sinard JH, Griffiths CT, Rheinwald JG. The mesothelial keratins: a new family of cytoskeletal proteins identified in cultured mesothelial cells and nonkeratinizing epithelia. Cell. 1982 Dec;31(3 Pt 2):693–703. [PubMed]

Articles from The Journal of Cell Biology are provided here courtesy of The Rockefeller University Press