Biochemical and Biophysical Research Communications
Apoptosis-associated tyrosine kinase is a Cdk5 activator p35 binding protein
Section snippets
Materials and methods
Yeast two-hybrid system and construction of vectors for screening. The yeast two-hybrid screening was performed using MATCHMAKER Two-Hybrid System 2 (Clontech, Palo Alto, CA). pAS2-p35 was constructed by cutting pCMV-human p35 with EcoRI and NotI, and cloned into the EcoRI/NotI site of pAS2. Foetal and adult human brain cDNA libraries (Clontech) were cloned into pACT2. Yeast strain Y190 was transformed with pAS2-p35 and pACT2-cDNA library using a lithium acetate method. β-Galactosidase activity
Screening of a splice variant of the human homologue of AATYK as a p35 binding protein by the yeast two-hybrid system
An isolated clone was found to be identical to the reported nucleotide sequence 1225–5140 of KIAA0641, except for a 263 bp deletion, upon DNA sequencing and homology search. The clone encoded 477 amino acids corresponding with the internal 272–730 amino acids of KIAA0641 (Fig. 1A), followed by 19 amino acids unique to this clone after splicing (indicated by grey in Fig. 1A and by bold in Fig. 1B). KIAA0641 is a human homologue of apoptosis-associated tyrosine kinase AATYK [15], [16], but its
Discussion
Cdk5/p35 plays important roles in brain development, synaptic activity, and neuronal cell death. However, how Cdk5 functions in these neuronal activities has not yet been understood in detail. Identification of proteins interacting with Cdk5 or p35 is an important step to uncover possible molecular mechanisms. The protein (hAATYKs-p35BP) cloned from the human foetal brain cDNA library was a splice variant of KIAA0641, a human homologue of AATYK [15], [16]. KIAA0641 (hAATYK) and its short splice
Acknowledgements
We thank Dr. James Bibb at University of Texas Southwestern Medical Center for critical reading of the manuscript, Dr. L.-H. Tsai at Harvard Medical School for providing cDNAs of p35 and Cdk5, and Drs. H. Nagase and O. Ohara at Kazusa DNA Research Institute for providing KIAA0641 cDNA. This work was supported by Grants-in-Aid for Scientific Research on Priority Areas (C), Advanced Brain Science Project from the Ministry of Education, Culture, Sports, and Science and Technology, of Japan.
References (26)
- et al.
Cdk5 behind the wheel: a role in trafficking and transport?
Trends Cell Biol.
(2002) - et al.
p35, the neuronal-specific activator of cyclin-dependent kinase 5 (Cdk5) is degraded by the ubiquitin–proteasome pathway
J. Biol. Chem.
(1998) - et al.
Okadaic acid-stimulated degradation of p35, an activator of CDK5, by proteasome in cultured neurons
Biochem. Biophys. Res. Commun.
(1998) - et al.
Reconstitution of neuronal Cdc2-like kinase from bacteria-expressed Cdk5 and an active fragment of the brain-specific activator. Kinase activation in the absence of Cdk5 phosphorylation
J. Biol. Chem.
(1995) - et al.
Identification of functional domains in the neuronal Cdk5 activator protein
J. Biol. Chem.
(1997) - et al.
Association of neurofilament proteins with neuronal Cdk5 activator
J. Biol. Chem.
(1998) - et al.
Identification of ribosomal protein L34 as a novel Cdk5 inhibitor
Biochem. Biophys. Res. Commun.
(1999) - et al.
Cables links Cdk5 and c-Abl and facilitates Cdk5 tyrosine phosphorylation, kinase upregulation, and neurite outgrowth
Neuron
(2000) - et al.
Identification of a neuronal Cdk5 activator-binding protein as Cdk5 inhibitor
J. Biol. Chem.
(2002) - et al.
Pctairel interacts with p35 and is a novel substrate for Cdk5/p35
J. Biol. Chem.
(2002)
Calpain-dependent proteolytic cleavage of the p35 cyclin-dependent kinase 5 activator to p25
J. Biol. Chem.
Alternative pre-mRNA splicing: the logic of combinatorial control
Trends Biochem Sci.
Differential expression and function of apoptosis-associated tyrosine kinase (AATYK) in the developing mouse brain
Mol. Brain Res.
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Present address: Technical Services Department, Promega K.K., Tokyo 103-0011, Japan.
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Present address: Division of Molecular Biology, Department of Molecular and Cellular Biology, Kobe University Graduate School of Medicine, Kobe 650-0017, Japan.
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Present address: Graduate School of Biological Sciences, Nara Institute of Science and Technology, Nara 630-0101, Japan.
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Present address: Horizontal Medical Research Organization, Graduate School of Medicine, Kyoto University, Kyoto 606-8501, Japan.