Understanding The Cytokeratin Family

Cytokeratins are a complex family of proteins that are the key components of the cytoskeleton of epithelial cells, forming the intermediate filaments characteristic of that structure.

There are more than 50 recognised members of the cytokeratin family in humans, although many are restricted to expression in hair follicles and are only recently discovered. This blog won’t include discussion of those, but will instead focus on the more traditional epithelial cell cytokeratin family members that have found so much utility in defining tissue types in IHC applications.

Cytokeratin nomenclature

Possibly one of the most confusing aspects of the cytokeratin family is the different nomenclature that is used.  Several of the terms used to describe cytokeratins are used interchangeably, which we will summarise as follows.

Cytokeratin vs. keratin The term Cytokeratin was first used in the 1970’s when the constituent proteins of the intermediate filaments were identified (1). The term Keratin has been more formally used since 2006 (2), but in practice both are used interchangeably.  It is worth noting that the gene names use the nomenclature KRT

Acidic vs. Basic  Descriptions of cytokeratin according to their pI classify them into two families. It is worth noting that some authors also use the term “neutral” for cytokeratins that others describe as “basic”. Importantly the acidic/basic nomenclature overlaps directly with that of size…..

LMW vs. HMW  A very common grouping of the cytokeratins is into so called “low molecular weight” of “high molecular weight” families. If you understand that the size of cytokeratins decreases as the family number increases you’ll follow this fairly easily, although the differentiation is arguably fairly arbitrary.

Type I vs Type II A further grouping is into so-called Type I and Type II, another arbitary nomenclature that aligns with the charge based and size nomenclatures

With all of these different terminologies it is not surprising that confusion arises. Interestingly perhaps the clearest grouping is that some family members are found on Chromosome 17q and others on 12q.  The table below attempts to classify the different epithelial cytokeratins using all of these groupings.

Cytokeratin specific antibodies

There are many antibodies available that recognise cytokeratins. Some of these antibodies are highly specific, and will detect just a single cytokeratin, whilst others have a broader reactivity pattern. Immuquest are pleased to offer a range of cytokeratin specific antibodies to support studies of CK expression in different tissues, and to help identify specific tumour types.

References

1. Franke, W.W. et al (1979) Cell. Biol. 81:570-580
2. Schweizer,J. et al (2006) Cell Biol 174:169-174