Molecular neuroscienceStructural and functional analysis of the apoptosis-associated tyrosine kinase (AATYK) family
Section snippets
Experiments on animals
All animal experiments were carried out in accordance with the RIKEN guidelines for animal use and the U.S. National Institutes of Health Guide for the Care and Use of Laboratory Animals. All efforts were made to minimize the number of animals used and their suffering.
Identification and cloning of the AATYK family genes
For the cloning of the 5′ region of AATYK1 mRNA, we screened the mouse adult brain library, 5′ rich-pME18S library, which was constructed by Oligo-Capping method (Suzuki et al., 1997), based on the polymerase chain reaction (PCR)
Structure of the AATYK family members
We previously isolated the AATYK1 gene from cultured Purkinje cells and showed the existence of sequence diversity in the 5′ region among several cloned cDNAs (Tomomura et al., 2001). The major form of AATYK1 clones was AATYK1A, which encodes the same open reading frame (ORF) as that cloned in myeloid cells (Gaozza et al 1997, Baker et al 2001). An alternative-splicing variant form of the AATYK1 (B-AATYK) clone containing an additional in-frame 5′-end sequence was also isolated from mouse
Discussion
In this study, we characterized the mouse AATYK family proteins, AATYK1A, AATYK1B, AATYK2, and AATYK3. AATYK1A and AATYK1B are produced from the same AATYK1 gene by alternative splicing. We showed that AATYK1B, 2, and 3 have the SP and TM domains at the N-terminal region, whereas AATYK1A lacks the SP and TM region. TM(+)AATYKs (1B, 2, and 3) are integral membrane proteins, whereas TM(−)AATYK1A is a peripheral membrane protein anchoring via the N-terminal palmitoylation and is the predominant
Conclusion
In conclusion, our study indicates that the AATYK family consists of three distinct types, AATYK1, 2, and 3, and two alternative splicing types in AATYK1, TM(+) and TM(−) types, with slightly different patterns in their regional and subcellular localization in the brain as well as in their developmental and tissue-specific expression. These subtle differences in the expression patterns and functional properties within the AATYK family may be involved in the fine regulation of neuronal functions
Acknowledgments
We thank Professor Shinichi Hisanaga (Tokyo Metropolitan University), Dr. Akira Sato (RIKEN Genome Center) and Dr. Liria M. Masuda-Nakagawa (University of Tokyo) for their critical comments and reading. We also thank Dr. Masaki Kumai (RIKEN BSI Research resource center) for his excellent service in antibody production and Ms. Emiko Suga for her technical assistance. This research was supported by a grant-in-aid for Scientific Research from the Japanese Ministry of Education, Culture, Sports,
References (35)
- et al.
Structures of axon guidance molecules and their neuronal receptors
Adv Protein Chem
(2004) - et al.
Site-directed mutagenesis by overlap extension using the polymerase chain reaction
Gene
(1989) - et al.
Apoptosis-associated tyrosine kinase is a Cdk5 activator p35 binding protein
Biochem Biophys Res Commun
(2003) - et al.
Neuronal cyclin-dependent kinase 5: role in nervous system function and its specific inhibition by the Cdk5 inhibitory peptide
Biochim Biophys Acta
(2004) Tau and src family tyrosine kinases
Biochim Biophys Acta
(2005)- et al.
Brain actin-associated protein phosphatase 1 holoenzymes containing spinophilin, neurabin, and selected catalytic subunit isoforms
J Biol Chem
(1999) - et al.
Regulation of neuronal morphogenesis and synaptic function by Abl family kinases
Curr Opin Neurobiol
(2003) - et al.
The role of protein phosphatase-1 in the modulation of synaptic and structural plasticity
FEBS Lett
(2004) - et al.
A novel kinase, AATYK induces and promotes neuronal differentiation in a human neuroblastoma (SH-SY5Y) cell line
Brain Res Mol Brain Res
(2000) Fatty acylation of proteins: new insights into membrane targeting of myristoylated and palmitoylated proteins
Biochim Biophys Acta
(1999)
Cdk5 behind the wheel: a role in trafficking and transport?
Trends Cell Biol
Construction and characterization of a full length-enriched and a 5′-end-enriched cDNA library
Gene
Apoptosis-associated tyrosine kinase (AATYK) has differential Ca2+-dependent phosphorylation states in response to survival and apoptotic conditions in cerebellar granule cells
J Biol Chem
Differential expression and function of apoptosis-associated tyrosine kinase (AATYK) in the developing mouse brain
Brain Res Mol Brain Res
A novel transmembrane Ser/Thr kinase complexes with protein phosphatase-1 and inhibitor-2
J Biol Chem
Peptide microarray analysis of substrate specificity of the transmembrane Ser/Thr kinase KPI-2 reveals reactivity with cystic fibrosis transmembrane conductance regulator and phosphorylase
Mol Cell Proteomics
Inhibition of protein palmitoylation, raft localization, and T cell signaling by 2-bromopalmitate and polyunsaturated fatty acids
J Biol Chem
Cited by (47)
LMTK2-mediated phosphorylation regulates CFTR endocytosis in human airway epithelial cells
2014, Journal of Biological ChemistryCitation Excerpt :Still, it is unknown whether CFTR is an LMTK2 substrate in airway epithelial cells. LMTK2 also known as kinase/phosphatase/inhibitor-2 (KPI2), brain-enriched kinase (BREK), apoptosis-associated tyrosine kinase (AATYK2), and cyclin-dependent kinase-5 (cdk5/p35) regulated kinase, is a member of the lemur family of membrane-anchored kinases (37–41). Despite the original prediction to be a dual-specificity serine-threonine/tyrosine kinase, studies have shown that purified LMTK2 kinase domain phosphorylates only serine and threonine residues (36, 37, 39).
The LMTK-family of kinases: Emerging important players in cell physiology and pathogenesis
2021, Biochimica et Biophysica Acta - Molecular Basis of DiseaseCitation Excerpt :Sequence analysis and experimental evidence indicate an N-terminal signal peptide and a transmembrane (TM) region. Indeed, topological studies using fluorescence protease protection experiments concluded that LMTK2 is an integral membrane protein with two transmembrane domains, positioning both the N- and C-terminals in the cytoplasm [2,3]. Similar studies for LMTK1 and LMTK3 have not been conducted; therefore, their exact membrane topology remains elusive.
Overexpression of lemur tyrosine kinase-2 protects neurons from oxygen-glucose deprivation/reoxygenation-induced injury through reinforcement of Nrf2 signaling by modulating GSK-3β phosphorylation
2020, Biochemical and Biophysical Research CommunicationsCitation Excerpt :Therefore, scavenging ROS represents a novel therapeutic strategy for treatment of cerebral ischemia/reperfusion injury. Lemur tyrosine kinase 2 (LMTK2) is a member of lemur kinase proteins, a group of transmembrane serine/threonine-protein kinases [6,7]. LMTK2 is ubiquitously expressed in various tissues and plays a crucial role in various biological processes [8–10].
A revised nomenclature for the lemur family of protein kinases
2024, Communications BiologyDifferential Gene Expression in the Penile Cavernosum of Streptozotocin-Induced Diabetic Rats
2023, International Neurourology JournalTectorigenin mediates miR-338-3p/aatk axis to prevent fulminant hepatic failure
2023, Journal of Biological Regulators and Homeostatic Agents