Cytokeratin, pan Products

Cytokeratins are a family of intermediate filamentous proteins that are expressed by epithelial cells (1,2). Cytokeratins range in size with a theoretic molecular weight varying from approximately 40 kDa to 68 kDa (2,3). The cytokeratin family consists of 20 polypeptides that are further divided into two main groups based on isoelectric point and molecular weight (1-3). The type I group are smaller, acidic polypeptides designated as cytokeratin 9 through cytokeratin 20 (CK9 - CK20) (1-4). Conversely, CK1 - CK8 belong to the type II group, classified as larger, basic or neutral polypeptides (1-4). Structurally, cytokeratins have homologous basic structure with other intermediate filaments; they possess a 300-315 amino acid (aa) central helical region that consists of four conserved domains (1A, 2A, 1B, and 2B) which are separated by linker domains (L1, L12, and L2) (1,5). Additionally, flanking this central region, both the amino- and carboxyl-terminal ends have a homologous subdomain (H), a variable domain (V), and charged end subdomains (E) (1). Furthermore, the central rod of one cytokeratin monomer binds with another monomer to form a coiled-coil dimer which subsequently binds another dimer to form a tertramer (3). Finally, many tetramers join together to ultimately form an intermediate filament of approximately 10nm in diameter (1-3, 5). Cytokeratins are expressed as pairs, typically with a type I and type II member; for example, CK10 pairs with CK1 (1,3).

Epithelial cells express multiple subtypes of cytokeratins which can be used to classify epithelial cell type or differentiation status, as well tumor progression or diagnosis (2). Cytokeratins are important for both stability and integrity of epithelial cells and function in intracellular signaling, from wound healing to apoptosis (1). Cytokeratins are useful immunohistochemistry tumor markers and antibodies to cytokeratins are a common pathological tool (1,3,6). Cytokeratin pan antibody is an antibody cocktail mixture that can detect multiple cytokeratins and reacts to multiple epithelial tissues (1,3,6). For example, AE-1/AE-3 is a commonly used specific pan cytokeratin that detects cytokeratins 1-8, 10, 14-16 and 19 (1,3,6).

Given the role of cytokeratins in the structural integrity of epithelial cells, mutations in cytokeratins have been shown to play a role in a variety of human diseases including epidermolysis bullosa simplex (EBS) (4,5). EBS is an autosomal dominant disorder that is caused by missense mutations in either CK5 or CK14 (5). Other known cytokeratin-related disorders include bullous ichthyosis, a skin disorder characterized by redness, blistering, and hyperkeratosis, and epidermolytic palmoplantar keratoderma (EPPK), which results in hyperkeratosis on the palms and soles of the body (7).

References

1. Awasthi, P., Thahriani, A., Bhattacharya, A., Awasthi, P., & Keratins, B. A. (2016). Keratins or cytokeratins: a review article. Journal of Advanced Medical and Dental Sciences Research. https://10.21276/jamdsr.2016.4.4.30

2. Southgate, J., Harnden, P., & Trejdosiewicz, L. K. (1999). Cytokeratin expression patterns in normal and malignant urothelium: a review of the biological and diagnostic implications. Histology and histopathology. https://doi.org/10.14670/HH-14.657

3. Belaldavar, C., Mane, D. R., Hallikerimath, S., Kale, A. D. (2016). Cytokeratins: Its role and expression profile in oral health and disease. Journal of Oral and Maxillofacial Surgery, Medicine, and Pathology. https://doi.org/10.1016/j.ajoms.2015.08.001.

4. Linder S. (2007). Cytokeratin markers come of age. Tumour biology : the journal of the International Society for Oncodevelopmental Biology and Medicine. https://doi.org/10.1159/000107582

5. Jacob, J. T., Coulombe, P. A., Kwan, R., & Omary, M. B. (2018). Types I and II Keratin Intermediate Filaments. Cold Spring Harbor perspectives in biology. https://doi.org/10.1101/cshperspect.a018275

6. Ordonez N. G. (2013). Broad-spectrum immunohistochemical epithelial markers: a review. Human pathology. https://doi.org/10.1016/j.humpath.2012.11.016

7. McLean, W. H., & Moore, C. B. (2011). Keratin disorders: from gene to therapy. Human molecular genetics. https://doi.org/10.1093/hmg/ddr379