MNB/DYRK1A phosphorylation regulates the interactions of synaptojanin 1 with endocytic accessory proteins.
MNB/DYRK1A is a proline-directed serine/threonine kinase implicated in Down syndrome (DS). In an earlier screening, two proteins from adult rat brain, one 100kDa and the other 140 kDa, were found to be prominently phosphorylated by the kinase. The 100-kDa protein was previously characterized as an isoform of dynamin 1. In this study, we identified the 140-kDa protein as synaptojanin 1 (SJ1). MNB/DYRK1A phosphorylates SJ1 at multiple sites and produces complex behaviors in binding to amphiphysin 1 and intersectin 1 (ITSN1). However, the phosphorylation has little effect on the phosphatidylinositol phosphatase activity of SJ1. These results suggest that MNB/DYRK1A is involved in regulating the recruitment activity but not the phosphatase activity of SJ1. Our findings may be especially important in the etiology of DS because MNB/DYRK1A, SJ1, and ITSN1 are all located at or near the region of human chromosome 21, which is postulated to be involved in the disease.
Adayev
Tatyana
T
Molecular Biology Department, NYS Institute for Basic Research in Developmental Disabilities, Staten Island, NY 10314, USA.
Chen-Hwang
Mo-Chou
MC
Murakami
Noriko
N
Wang
Rong
R
Hwang
Yu-Wen
YW
D033942:Adaptor Proteins, Vesicular Transport / Q000378:metabolism*; D000595:Amino Acid Sequence; D000818:Animals; D002478:Cells, Cultured; D004705:Endocytosis; D006801:Humans; D000072181:Inositol Polyphosphate 5-Phosphatases; D051379:Mice; D008969:Molecular Sequence Data; D009419:Nerve Tissue Proteins / Q000378:metabolism*; D010744:Phosphoric Monoester Hydrolases / Q000378:metabolism*; D010766:Phosphorylation; D017346:Protein Serine-Threonine Kinases / Q000378:metabolism*; D011505:Protein-Tyrosine Kinases; D051381:Rats; D013379:Substrate Specificity; D000097603:Dyrk Kinases
D033942:Adaptor Proteins, Vesicular Transport; D000072181:Inositol Polyphosphate 5-Phosphatases; D009419:Nerve Tissue Proteins; D010744:Phosphoric Monoester Hydrolases; D017346:Protein Serine-Threonine Kinases; D011505:Protein-Tyrosine Kinases; D000097603:Dyrk Kinases; C115919:intersectin 1; C097702:synaptojanin