Critical role of the CMGC insert sequence for tyrosine autophosphorylation in the protein kinase DYRK1B.

ABSTRACT: Many CMGC group kinases require phosphorylation of a conserved tyrosine residue in the activation loop to achieve catalytic activity. DYRK family members use a distinctive mechanism involving constitutive cis-autophosphorylation of this tyrosine. The structural basis of this process has remained unclear, as it occurs while the kinase is still in an inactive conformation, and the tyrosine does not match the known substrate consensus of DYRKs. Here, we exploited the different autophosphorylation capacities of the paralogs DYRK1A and DYRK1B to define structural determinants of this process. DYRK1A efficiently autophosphorylates even in cell-free systems, whereas DYRK1B does not. Using domain swaps and point mutations, we identify the CMGC insert in the C-terminal lobe and two adjacent proline

SUBMITTER: Detro-Dassen S 

PROVIDER: S-EPMC12738607 | biostudies-literature | 2025 Dec

REPOSITORIES: biostudies-literature