Alternative titles; symbols
HGNC Approved Gene Symbol: PLEK
Cytogenetic location: 2p14 Genomic coordinates (GRCh38) : 2:68,365,282-68,397,453 (from NCBI)
In platelets, agonists that stimulate phosphoinositide turnover cause the rapid phosphorylation of a protein of apparent relative molecular mass 40,000-47,000, called P47, by protein kinase C. Tyers et al. (1988) isolated human P47 clones by immunologic screening of a lambda-gt11 cDNA library from a promyelocytic leukemia cell line. A 1,050 basepair open reading frame that could encode the protein in question was confirmed by comparison with peptide sequences from platelet P47 and by expression of the putative P47 in E. coli and in vitro. The P47 sequence appeared to have been conserved throughout vertebrate evolution and was not similar to any other known sequence, including lipocortin (151690). Based on its specific expression in platelets and various differentiated white blood cells, Tyers et al. (1988) proposed the name pleckstrin for platelet and leukocyte C kinase substrate and for the KSTR string of amino acids in the sequence KFARKSTRRSIR, the probable phosphorylation site. Tyers et al. (1989) reported the pleckstrin sequence. They deduced a molecular mass of 40,087 kD.
By differential display comparison of murine epidermal promotion-sensitive and -resistant cell lines after exposure to a tumor promoter, phorbol ester TPA, Cmarik et al. (2000) observed preferential expression in promotion-resistant cells of a cDNA encoding Plek. Northern blot analysis detected a 3.6-kb Plek transcript in mouse heart, lung, and spleen. Mouse Plek shares 91% amino acid identity with human PLEK.
By in situ hybridization, Lezirovitz et al. (2020) found Plek mRNA expression in mouse dorsal root ganglion on postnatal day (P)7. No Plek expression was detected in the inner ear or cochlear hair cells at this age. In early adulthood (P21 to P35), Plek showed expression in the organ of Corti and in spiral ganglion neurons (SGNs), as well as in the spiral limbus fibrocytes. Analysis of protein expression showed that by early adulthood (P21 to P35), Plek antibody strongly labeled fibrocytes lining the perilymphatic face of the bony spiral limbus, and cells within stria vascularis and the organ of Corti displayed diffuse fluorescence. Cell bodies of SGNs were also distinctly immunolabeled. Noting that expression of Plek localized to key loci within the cochlea as well as within the primary afferent pathway, the authors suggested that Plek might play an important role in the inner ear.
Using an interspecific backcross panel, Cmarik et al. (2000) mapped the mouse Plek gene to the proximal part of chromosome 11 in a region showing homology of synteny to human 2p, where they stated the PLEK gene has been mapped.
Cmarik, J. L., Hegamyer, G., Gerrard, B., Dean, M., Colburn, N. H. cDNA cloning and mapping of mouse pleckstrin (Plek), a gene upregulated in transformation-resistant cells. Genomics 66: 204-212, 2000. [PubMed: 10860665] [Full Text: https://doi.org/10.1006/geno.2000.6210]
Lezirovitz, K., Vieira-Silva, G. A., Batissoco, A. C., Levy, D., Kitajima, J. P., Trouillet, A., Ouyang, E., Zebarjadi, N., Sampaio-Silva, J., Pedroso-Campos, V., Nascimento, L. R., Sonoda, C. Y., and 9 others. A rare genomic duplication in 2p14 underlies autosomal dominant hearing loss DFNA58. Hum. Molec. Genet. 29: 1520-1536, 2020. [PubMed: 32337552] [Full Text: https://doi.org/10.1093/hmg/ddaa075]
Tyers, M., Haslam, R. J., Rachubinski, R. A., Harley, C. B. Molecular analysis of pleckstrin: the major protein kinase C substrate of platelets. J. Cell. Biochem. 40: 133-145, 1989. [PubMed: 2768345] [Full Text: https://doi.org/10.1002/jcb.240400202]
Tyers, M., Rachubinski, R. A., Stewart, M. I., Varrichio, A. M., Shorr, R. G. L., Haslam, R. J., Harley, C. B. Molecular cloning and expression of the major protein kinase C substrate of platelets. Nature 333: 470-473, 1988. [PubMed: 2897630] [Full Text: https://doi.org/10.1038/333470a0]