Keratin intermediate filaments in epithelial cells (red stain).

Cytokeratins are proteins of keratin-containing intermediate filaments found in the intracytoplasmic cytoskeleton of epithelial tissue. The term "cytokeratin" began to be used in the late 1970s (for example, see "Intermediate-sized filaments of human endothelial cells" by Franke, Schmid, Osborn and Weber[1]) when the protein subunits of keratin intermediate filaments inside cells were first being identified and characterized. In 2006 a new systematic nomenclature for keratins was created and now the proteins previously called "cytokeratins" are simply called keratins.[2] Over 25,000 published articles exist in the biomedical research literature that used the term "cytokeratin".



Micrograph showing low molecular weight cytokeratin (LMWCK) staining of intermediate trophoblast (placental tissue) and endometrial glands.

There are two types of cytokeratins: the acidic type I cytokeratins and the basic or neutral type II cytokeratins. Cytokeratins are usually found in pairs comprising a type I cytokeratin and a type II cytokeratin. Basic or neutral cytokeratins include CK1, CK2, CK3, CK4, CK5, CK6, CK7, CK8 and CK9. Acidic cytokeratins are CK10, CK12, CK 13, CK14, CK16, CK17, CK18, CK19 and CK20. The cytokeratins cannot be divided into low versus high molecular weight solely based on their charge. Expression of these cytokeratins is frequently organ or tissue specific. As an example, CK7 is typically expressed in the ductal epithelium of the genitourinary (GU) tract and CK20 most commonly in the gastrointestinal (GI) tract.[3] Histopathologists employ such distinctions to detect the cell of origin of various tumors.

The subsets of cytokeratins which an epithelial cell expresses depends mainly on the type of epithelium, the moment in the course of terminal differentiation and the stage of development. Thus this specific cytokeratin fingerprint allows the classification of all epithelia upon their cytokeratin expression profile. Furthermore this applies also to the malignant counterparts of the epithelia (carcinomas), as the cytokeratin profile tends to remain constant when an epithelium undergoes malignant transformation. The main clinical implication is that the study of the cytokeratin profile by immunohistochemistry techniques is a tool of immense value widely used for tumor diagnosis and characterization in surgical pathology.[4]

Cytokeratin Sites
Cytokeratin 4
Cytokeratin 7
Cytokeratin 8
  • Glandular epithelia of the digestive, respiratory and urogenital tracts, both endocrine and exocrine cells, as well as mesothelial cells
  • Adenocarcinomas originating from those above[5]
Cytokeratin 10
Cytokeratin 13
  • Non-keratinized squamous epithelia, except cornea[5]
Cytokeratin 14
  • Basal layer of stratified and combined epithelia[5]
Cytokeratin 18
  • Glandular epithelia of the digestive, respiratory, and urogenital tracts, both endocrine and exocrine cells, as well as mesothelial cells
  • Adenocarcinomas originating from those above[5]
Cytokeratin 19
  • Glandular-type epithelia [5]
  • Carcinomas[5]

Does not react with hepatocytes and hepatocellular carcinoma[5]

Cytokeratin 20
  • Glandular-type epithelia. Signet ring/round clear cells [5]
  • GI stromal tumor (Krukenberg)[5]

Molecular biology

The cytokeratins are encoded by a family encompassing 30 genes. Among them, 20 are epithelial genes and the remaining 10 are specific for trichocytes.

All cytokeratin chains are composed of a central α-helix-rich domain (with a 50-90% sequence identity among cytokeratins of the same type and around 30% between cytokeratins of different type) with non-α-helical N- and C-terminal domains. The α-helical domain has 310-150 amino acids and comprises four segments in which a seven-residue pattern repeats. Into this repeated pattern, the first and fourth residues are hydrophobic and the charged residues show alternate positive and negative polarity, resulting in the polar residues being located on one side of the helix. This central domain of the chain provides the molecular alignment in the keratin structure and makes the chains form coiled dimers in solution.

The end-domain sequences of type I and II cytokeratin chains contain in both sides of the rod domain the subdomains V1 and V2, which have variable size and sequence. The type II also presents the conserved subdomains H1 and H2, encompassing 36 and 20 residues respectively. The subdomains V1 and V2 contain residues enriched by glycines and/or serines, the former providing the cytokeratin chain a strong insoluble character and facilitating the interaction with other molecules. These terminal domains are also important in the defining the function of the cytokeratin chain characteristic of a particular epithelial cell type.

Two dimers of cytokeratin groups into a keratin tetramer by anti-parallel binding. This cytokeratin tetramer is considered to be the main building block of the cytokeratin chain. By head-to-tail linking of the cytokeratin tetramers, the protofilaments are originated, which in turn intertwine in pairs to form protofibrils. Four protofibrils give place to one cytokeratin filament.

Cell biology

In the cytoplasm, the keratin filaments conform a complex network which extends from the surface of the nucleus to the cell membrane. Numerous accessory proteins are involved in the genesis and maintenance of such structure.

This association between the plasma membrane and the nuclear surface provides important implications for the organization of the cytoplasm and cellular communication mechanisms. Apart from the relatively static functions provided in terms of supporting the nucleus and providing tensile strength to the cell, the cytokeratin networks undergo rapid phosphate exchanges mediated depolymerization, with important implications in the more dynamic cellular processes such as mitosis and post-mitotic period, cell movement and differentiation.

Cytokeratins interact with desmosomes and hemidesmosomes, thus collaborating to cell-cell adhesion and basal cell-underlying connective tissue connection.

The intermediate filaments of the eukaryotic cytoskeleton, which the cytokeratins are one of its three components, have been probed to associate also with the ankyrin and spectrin complex protein network that underlies the cell membrane.

External links


  1. ^ Franke WW, Schmid E, Osborn M, Weber K (1979). "Intermediate-sized filaments of human endothelial cells". J Cell Biol. 81 (3): 570–580. doi:10.1083/jcb.81.3.570. PMC 2110384. PMID 379021. 
  2. ^ Schweizer J, Bowden PE, Coulombe PA, Langbein L, Lane EB, Magin TM, Maltais L, Omary MB, Parry DA, Rogers MA, Wright MW (2006). "New consensus nomenclature for mammalian keratins". J Cell Biol. 174 (2): 169–174. doi:10.1083/jcb.200603161. PMC 2064177. PMID 16831889. 
  3. ^ CURRENT Diagnosis & Treatment: Obstetrics & Gynecology 2011. Chapter 52. Premalignant & Malignant Disorders of the Ovaries & Oviducts. Kathleen M. Brennan, MD, Vicki V. Baker, MD, & Oliver Dorigo, MD
  4. ^ Walid MS, Osborne TJ, Robinson JS (2009). "Primary brain sarcoma or metastatic carcinoma?". Indian J Cancer 46 (2): 174–175. doi:10.4103/0019-509X.49160. PMID 19346656. 
  5. ^ a b c d e f g h i j k l m MUbio > MONOCLONAL ANTIBODIES TO CYTOKERATINS Retrieved October 2010

Wikimedia Foundation. 2010.

Игры ⚽ Поможем написать реферат

Look at other dictionaries:

  • Cytokeratin — Keratinfilamente in einer Tumorzelle, fluoreszenzmikroskopisch dargestellt Keratin (von griech. kéras, Genitiv kératos = Horn) oder Hornsubstanz ist ein Sammelbegriff für verschiedene wasserunlösliche Faserproteine, die von menschlichen oder… …   Deutsch Wikipedia

  • Cytokeratin-21-Fragment — CYFRA 21 1 Le Cyfra 21 1 est un marqueur tumoral qui, en dosant un fragment de cytokératine 19 (Cytokeratin 21 Fragment), permet la surveillance évolutive des cellules cancéreuses pulmonaires (carcinome épidermoïde). Il n est pas utile pour le… …   Wikipédia en Français

  • cytokeratin(s) — Generic name for the intermediate filament proteins of epithelial cells …   Dictionary of molecular biology

  • cytokeratin — noun Either of several forms of keratin found in the intracytoplasmic cytoskeleton of epithelial tissue …   Wiktionary

  • cytokeratin — SYN: keratin. * * * cy·to·ker·a·tin (si″to kerґə tin) one of the two types of keratin normally found in human tissue, constituting a group of proteins; these are normally found in keratin filaments. Called also soft keratin …   Medical dictionary

  • soft keratin — cytokeratin …   Medical dictionary

  • Keratin 19 — Identifiers Symbols KRT19; CK19; K19; K1CS; MGC15366 External IDs OMIM …   Wikipedia

  • Keratin 13 — Identifiers Symbols KRT13; CK13; K13; MGC161462; MGC3781 External IDs OMI …   Wikipedia

  • Keratin 18 — Identifiers Symbols KRT18; CYK18; K18 External IDs OMIM …   Wikipedia

  • Keratin — Not to be confused with kerogen, carotene, chitin, or creatine. Microscopy of keratin filaments inside cells. Keratin refers to a family of fibrous structural proteins. Keratin is the key structural material making up the outer layer of human… …   Wikipedia

Share the article and excerpts

Direct link
Do a right-click on the link above
and select “Copy Link”