ID OF MINIBRAIN KINASE/DUAL-SPECIFICITY YAK 1-RELATED KINASE 1A P-SITES IN DYN-

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This subproject is one of many research subprojects utilizing the resources provided by a Center grant funded by NIH/NCRR. The subproject and investigator (PI) may have received primary funding from another NIH source, and thus could be represented in other CRISP entries. The institution listed is for the Center, which is not necessarily the institution for the investigator. The minibrain kinase (Mnbk)/dual specificity Yak 1 related kinase (Dyrk1A) gene is localized in the q21.22 region of human chromosome 21 and it has been associated with the mental retardation of Down syndrome. Mnbk/Dyrk1A is a proline-directed Ser/Thr kinase which preferentially phosphorylates the sequence RPX(S/T)P. Previously, Mnbk/Dyrk1A was found to phosphorylate dynamin 1 and alter its interactions with SH3 domain-containing proteins (Chen-Hwang, M. C. et. al. J. Biol. Chem. 277: 17597-17604, 2002). In this study, we sought to determine the Mnbk/Dyrk1A phosphorylation sites in dynamin 1. By a combination of dynamin 1 deletion mutants and synthetic peptides, three potential Mnbk/Dyrk1A phosphorylation sites, Ser-778, -795 and -857, were identified. Phosphorylation at Ser-795 and -857 was subsequently confirmed in Mnbk/Dyrk1A-phosphorylated intact dynamin 1 by mass spectroscopy. A manuscript has been submitted for publication.