Exp Neurobiol.  2011 Mar;20(1):35-44. 10.5607/en.2011.20.1.35.

Dyrk1A Positively Stimulates ASK1-JNK Signaling Pathway during Apoptotic Cell Death

• Choi HK
• Chung KC

• KMID: 2165344
• DOI: http://doi.org/10.5607/en.2011.20.1.35

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.

Keyword

ASK1; cell death; Dyrk1A; JNK; signal transduction

MeSH Terms

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
Down Syndrome
MAP Kinase Kinase Kinase 5
Protein Kinases
Proteins
Transcription Factors
Tyrosine
alpha-Synuclein