Autoregulatory control of microtubule binding in doublecortin-like kinase 1

The microtubule-associated protein, doublecortin-like kinase 1 (DCLK1), is highly expressed in a range of cancers and prominent therapeutic target for inhibitors. physiological roles DCLK1 activity how it regulated remain elusive. Here, we analyze the role mammalian regulating microtubule binding. We found that autophosphorylates residue within its C-terminal tail to restrict prevent aberrant hyperphosphorylation microtubule-binding domain. Removal or mutation this causes an increase phosphorylation doublecortin domains, which abolishes Therefore, autophosphorylation at specific sites has diametric effects on molecule’s association with microtubules. Our results suggest mechanism by modulates tune affinity. These provide molecular insights future efforts related DCLK1’s cancer development progression.