Dyrk1A Positively Stimulates ASK1-JNK Signaling Pathway during Apoptotic Cell Death.
- Author:
Hyoung Kyoung CHOI
1
;
Kwang Chul CHUNG
Author Information
- Publication Type:Original Article
- Keywords: ASK1; cell death; Dyrk1A; JNK; signal transduction
- MeSH: alpha-Synuclein; Cell Death; Chromosomes, Human, Pair 21; Cytosol; Down Syndrome; Drosophila melanogaster; Humans; MAP Kinase Kinase Kinase 5; Neurogenesis; Protein Kinases; Proteins; Signal Transduction; Transcription Factors; Tyrosine
- From:Experimental Neurobiology 2011;20(1):35-44
- CountryRepublic of Korea
- Language:English
- Abstract: Dual-specificity tyrosine (Y)-phosphorylation-regulated protein kinase 1A (Dyrk1A) is the mammalian homologue of Drosophila melanogaster minibrain and its human gene is mapped to the Down syndrome critical region of chromosome 21. Dyrk1A phosphorylates several transcription factors, including NFAT and CREB and a number of cytosolic proteins such as APP, tau, and alpha-synuclein. Although Dyrk1A is involved in the control of cell growth and postembryonic neurogenesis, its potential role during cell death and signaling pathway is not clearly understood. In the present study, we show that Dyrk1A is activated under the condition of apoptotic cell death. In addition, Dyrk1A is coupled to JNK1 activation, and directly interacts with apoptosis signal-regulating kinase 1 (ASK1). Moreover, Dyrk1A positively regulates ASK1-mediated JNK1-signaling, and appears to directly phosphorylate ASK1. These data indicate that Dyrk1A regulates cell death through facilitating ASK1-mediated signaling events.
