Identification of signal transduction pathways affected by over-expression of the protein kinase DYRK1A

DYRK1A maps in 21q22.1 within the chromosomal region known as DSCR (Down syndrome critical region). The gene encodes a protein kinase able to phosphorylate serine, threonine and tyrosine residues and belongs to a protein kinase family with similar structural and functional characteristics. This family of proteins can be divided in two subfamilies: the HIPK subfamily with three members in humans, HIPK1, HIPK2 (PKM) and HIPK3 (ANPK, FIST), and the DYRK subfamily with five members in humans DYRK1A, DYRK1B, DYRK2, DYRK3 and DYRK4 and with homologous proteins in Drosophila (minibrain, DYRK2), Dictyostelium (YakA) and yeast (Yak1p). The limited information available for these proteins places them in cellular pathways that work coupling cell proliferation to cell differentiation.

We will focus in finding signal transduction pathways in which DYRK1A is involved. For that, a yeast-two hybrid screening has been performed that has lead to the identification of putative DYRK1A partners. We are currently involved in the characterization of the interactions.

DYRK1A has been described as a nuclear protein. However, the endogenous protein can behave not only as nuclear but also as a cytosolic protein. We would like to know which are the mechanisms that control the subcellular distribution of DYRK1A.