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Beschreibung

Serine/threonine-protein kinase DCLK1 (UniProt: O15075, also known as EC: 2.7.11.1, Doublecortin domain-containing protein 3A, Doublecortin-like and CAM kinase-like 1, Doublecortin-like kinase 1) is encoded by the DCLK1 (also known as DCAMKL1, DCDC3A, KIAA0369) gene (Gene ID: 9201) in human. DCLK1 is an integral component of plasma membrane and is highly expressed in fetal brain tissue and is also detectable in lung and liver. DCLK1 expression is reported to be critical for growth of human colon cancer cells and its expression is up-regulated in response to growth factors resulting in hyperproliferation. Both long (L) (~80-82 kDa) and short (S) (~45-50 kDa) isoforms of DCLK1 have been described. The long isoform of DCLK1 contains two N-terminal doublecortin domains, which bind microtubules, a C-terminal serine/threonine kinase domain with homology to CaM kinases, and a middle serine/proline rich domain that mediates protein interactions. The short isoform, DCLK1-S, has been reported in human colorectal cancer cells and in cancer stem cells, while normal colon cells express only the long isoform of DCLK1. The short isoforms lacks the two N-terminal doublecortin domains. Although DCLK1-S differs from the long isoform by only six amino-acids., this mono-specific antibody does not cross-react with the long isoform and is shown to specifically detect cancer stem cells. The short isoform is not a splice variant, but is expressed from an alternate beta promoter in intron V of the gene that results in the presence of the unique sequence of amino acids. These amino acids are absent in the long isoform, which is expressed by the alpha promoter in the 5&rsquo, region of the gene. It has been reported that the 5&prime, (alpha)-promoter of the human DCLK1 gene becomes epigenetically silenced during colon carcinogenesis, resulting in loss of expression of the canonical long isoform in human colorectal adenocarcinomas (hCRCs). Instead, hCRCs express the short isoform, DCLK1-S. Colon tumors and normal colons from mice only express the long isoform, since the epigenetics of colon carcinogenesis in mice is significantly different from that in humans.(Ref.:Sarkar,S et al.(2017).Lab.Invest.97(10):1245-1261,Sarkar,S.,et al.(2017).Mol.Cancer Res.15(12):1678-1691).