Overexpression of DYRK1A in down syndrome: Analysis of kinase activity

Abstract

DYRK1A (dual-specificity tyrosine phosphorylation regulated kinase 1A) is known to play critical roles in regulating numerous cellular functions like cell cycle, neuronal development, and immune homeostasis. Altered expression DYRK1A is implicated in Alzheimer's Disease and various features of Down Syndrome (DS). The DYRK1A gene is located on chromosome 21 and due to trisomy of this chromosome in DS, the level of DYRK1A is elevated in the gene-dosage dependent manner. Nevertheless, how an increase in DYRK1A protein level would affect its activity in DS remains to be determined. The question was examined by performing side by side comparison of protein levels and the activity of DYRK1A extracted from control and DS samples. We show that DYRK1A activity elevation in DS is in parallel to that of DYRK1A protein level regardless of the status of kinase phosphorylation. This suggests that DYRK1A catalytic activity in DS is mainly regulated by protein level.