Doublecortin-like kinase 1 (DCLK1)

Doublecortin-like kinase 1 (DCLK1) is a multi-domain protein classified as a serine/threonine kinase and a microtubule-associated protein, belonging to both the protein kinase superfamily and the doublecortin (DCX) family[2][3][6]. Its structure includes two N-terminal doublecortin domains responsible for microtubule binding and stabilization, and a C-terminal kinase domain mediating phosphorylation events involved in signal transduction[1][2][3][6]. Alternative promoter usage and splicing produces multiple isoforms with distinct functions and domain architectures[1][2]. DCLK1 is essential for neuronal migration and development, and outside the nervous system, it serves as a marker for cancer stem cells and regulates oncogenic pathways, particularly epithelial-mesenchymal transition and tumorigenesis in several human cancers[1][4][5]. Small-molecule inhibitors targeting the kinase domain (e.g., DCLK1-IN-1) have been developed for research and potential therapeutic applications, though safety concerns remain because of DCLK1's physiological roles in neurogenesis and tissue stem cells[3][6]. Upregulation or mutation of DCLK1 is associated with poor prognosis and aggressive tumor behavior in multiple cancer types, highlighting its importance as both a biomarker and a drug target[2][5].

Other names

DCAMKL1Serine/threonine-protein kinase DCLK1DCDC3AKIAA0369Doublecortin domain-containing protein 3ADoublecortin-like and CAM kinase-like 1CL1CLICK1

Small molecule inhibitors (e.g., DCLK1-IN-1) bind to the kinase domain and inhibit ATP binding, thus inhibiting kinase activity. Potential allosteric modulation via auto-inhibitory C-terminal domain