Cytokeratin filaments

Ward, W.S., Schmidt, W.N., Schmidt, C.A., and Hnilica, L.S. (1989) Cross-linking of Novikoff ascites hepatoma cytokeratin filaments. Biochemistry 24(16), 4429-4434. 

Klymkowsky, M. W., Maynell, L. A., and Nislow, C. (1991). Cytokeratin phosphorylation, cytokeratin filament severing and the solubilization of the maternal mRNA Vgl. J. Cell Biol. 114, 787-797. 

Fonseca E, Nesland JM, Hoie J, Sobrinho-Simoes M. Pattern of expression of intermediate cytokeratin filaments in the thyroid gland An immunohistochemical study of simple and stratified epithelial-type cytokeratins. Yirchows Arch. 1997 430 239-245. 

Fig. 10.28. Formation of a cytokeratin filament. The central rod of the keratin monomer is principally a-helical structure. A specific acidic keratin monomer combines with a specific basic keratin monomer to form a heterodimer coil (a coiled coil structure). Two dimers combine in antiparallel fashion to form a tetramer, and the tetramers combine head-to-tail to form pro to filaments. Approximately eight protofilaments combine to form a filament. The filament is thicker than actin filaments (called thin filaments or micro filaments) and thinner than microtubules (thick tubes) and is therefore called an intermediate filament.

Strnad, P, Windoffer, R., and Leube, R.E., In vivo detection of cytokeratin filament network breakdown in cells treated with the phosphatase inhibitor okadaic acid, Cell Tissue Res., 306, 211, 2001. 

Tissue-specific intermediate filaments have been classified into vimentin filaments, glial filaments, neurofilaments, desmin filaments and cytokeratin filaments. Although each type of filament is composed of a different protein, the various proteins demonstrate remarkable sequence homology. Their functions are unknown. There are at least nine different proteins associated with intermediate filaments. 

Cytokeratins are members of the intermediate filament class of cytoskeletal proteins. Cytokeratins are a large protein family comprising two subfamilies of polypeptides, i.e. acidic (type I) and basic (type II) ones. Cytokeratin form tetramers, consisting of two type I and two type II polypeptides arranged in pairs of laterally aligned coiled coils. The distribution of the different type I and II cytokeratins in normal epithelia and in carcinomas is differentiation-related and can be used for cell typing and identification. 

The five intermediate filaments and their respective tissues are listed in Table 3. Only the intermediate filament, cytokeratin, is selected as useful in the initial classification of tumors. The other intermediate filaments can cause diagnostic confusion because (1) they are usually not expressed in their poorly differentiated counterparts (especially GFAP, NFP, and Desmin) and (2) they are often coexpressed on many types of tumors. Poorly differentiated neuroectodermal tumors may often express more than two intermediate filaments. Vimentin demonstrates the most lineage infidelity. 

The components of the intermediate filaments belong to five related protein families. They are specific for particular cell types. Typical representatives include the cytokeratins, desmin, vimentin, glial fibrillary acidic protein (GFAP), and neurofilament. These proteins all have a rod-shaped basic structure in the center, which is known as a superhelix ( coiled coil see keratin, p. 70). The dimers are arranged in an antiparallel fashion to form tet-ramers. A staggered head-to-head arrangement produces protofilaments. Eight protofilaments ultimately form an intermediary filament. 

Cross reactivity may occur with some antibodies. Polyclonal CEA cross reacts with nonspecific cross-reactive antigens in granulocytes whereas the monoclonal version of this antibody does not. Some antibodies may cross react with common epitopes on different intermediate filaments such as cytokeratin antibodies with GFAP-expressing glial cells. 

Abnormal tissues The antibody labeled 17/20 sarcomas, 16/18 melanomas, 4/4 meningeomas, and 3/3 schwannomas, and was the sole intermediate filament present in these tumours. In addition, variable percentages (10 to 57 percent) of carcinomas, neuroendocrine carcinomas, neuroblastomas, thymomas and mesotheliomas were positive with the antibody. With the exception of the neuroblastomas, cytokeratin was coexpressed with vimentin in these tumours. Among adenocarcinomas, more than 50 percent of papillary carcinomas of the thyroid as well as renal, endometrial, ovarian and lung carcinomas were labeled by the antibody and coexpressed keratins and vimentin. 

More recent efforts now indicate that this activity is far more complex than the targeting of this single event, as different phenotypic responses readily occur across a panel of cell lines. While at this time it is difficult to determine if this discovery provides a drug target, it has become clear that development of systems that target intermediate filaments and their cytokeratin structures offers a new realm for small molecule discovery. 

Cytokeratin belongs to a family of intermediate filament proteins in epithelial cells. 

Cytokeratin Intermediate filament keratins found in epithelial tissue. There are two types of cytokeratins the acidic type 1 cytokeratins and the basic or neutral type 11 cytokeratins. Cytokeratins are thought to play a role in the activation of plasma prekallikrein and plasminogen. See Crewther, W.G., Fraser, R.D., Lennox, F.G., and Lindley, H., The chemistry of keratins, Adv. Protein Chem. 20, 191-346, 1965 Masri, M.S. and Friedman, M., Interactions of keratins with metal ions uptake profiles, mode of binding, and effects on the properties of wool, Arfv. Exp. Med. Biol. 48, 551-587,1974 Fuchs, E. and Green, H., Multiple keratins of cultured human epidermal cells are translated from different mRNA molecules. Cell 17, 573-582, 1979 ... 

Intermediate filaments (10 nm) are intermediate in diameter between microtubules (25 nm) and actin filaments (7 nm). Intermediate filaments are classified into five groups cytokeratin, desmin, vimentin, neural, and glial filaments (for review, see Lazarides, 1980). In skeletal muscle, there are both desmin and vimentin filaments. 

Five classes of intermediate filament proteins have been described, generally referred to as types I through V. Types I and II are the acidic and basic polypeptides, respectively, which comprise the keratins and cytokeratins, a family of heteropolymers that are abundant in epithelia. Type III consist of vimentin, desmin, glial fibrillary acidic protein, and peripherin. Of these, desmin has specific importance... 

Intermediate filaments have been shown to be caspase cleavage targets, including cytokeratin 18, which is cleaved principally by activated caspase 3. M30 (Boehringer-Mannheim), an antibody that specifically recognizes the cleaved fragment of cytokeratin 18, has been utilized in both immunofluorescence and flow cytometric analysis to demonstrate caspase activity (64,65). 

---