Apoptosis-associated tyrosine kinase is a Cdk5 activator p35 binding protein

Honma, Naoyuki; Asada, Akiko; Takeshita, Sen; Enomoto, Mariko; Yamakawa, Eiko; Tsutsumi, Koji; Saito, Taro; Satoh, Takaya; Itoh, Hiroshi; Kaziro, Yoshito; Kishimoto, Takeo; Hisanaga, Shin‐ichi

doi:10.1016/j.bbrc.2003.08.143

Cited by 25 publications

(21 citation statements)

References 26 publications

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“…A point that deserves further investigation is the potential contribution of miR-338-p host gene ATKK in the regulation of neuroblastoma. Since Cdk5 activator p35 was found to bind and phosphorylate AATK [27], and Cdk5 has been identified exerting a key role in promoting neuronal survival by regulating Akt activity through neuregulin/PI3K signalling pathway [28], therefore we speculate that ATKK may function through Cdk5/ATKK/Akt pathway to cooperate with miR-338-3p exerting its regulation effect in neuroblastoma. Since Cdk5 activator p35 was found to bind and phosphorylate AATK [27], and Cdk5 has been identified exerting a key role in promoting neuronal survival by regulating Akt activity through neuregulin/PI3K signalling pathway [28], therefore we speculate that ATKK may function through Cdk5/ATKK/Akt pathway to cooperate with miR-338-3p exerting its regulation effect in neuroblastoma.…”

Section: Discussionmentioning

confidence: 93%

miR‐338‐3p suppresses neuroblastoma proliferation, invasion and migration through targeting PREX2a

et al. 2013

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MicroRNAs (miRNA) can regulate cancer cell proliferation and metastasis. Here, we show that miR-338-3p is down-regulated in metastatic tumor tissues compared to primary tumors, and that that miR-338-3p can inhibit cell proliferation by inducing cell cycle arrest, as well as restrain cell migration and invasion. PREX2a is confirmed as a direct target of miR-338-3p. Knockdown of PREX2a inhibits cell proliferation, migration and invasion through the PTEN/Akt pathway. miR-338-3p-dependent inhibition of proliferation and invasion can be rescued by PREXa. Overall, this study demonstrates that miR-338-3p affects the PTEN/Akt pathway by down-regulating PREX2a. This newly identified function of miR-338-3p provides novel insights into neuroblastoma and may foster therapeutic applications.

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Section: Discussionmentioning

confidence: 93%

miR‐338‐3p suppresses neuroblastoma proliferation, invasion and migration through targeting PREX2a

et al. 2013

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“…AATYK2/cprk was isolated as a p35-binding protein using a yeast two-hybrid system [5], as was the case for AATYK1 [15]. The p35-binding region of both AATYK1A and AATYK2/cprk is adjacent to the kinase domain in the carboxy terminal, which exhibits some amino-acid sequence similarity [1].…”

Section: Discussionmentioning

confidence: 99%

“…Cdk5/p35 plays a role in a variety of neuronal activities, including neuronal migration, neurite extension, endocytic pathway, synaptic plasticity, and neuronal death in neurodegenerative diseases [12], [13], [14]. We reported the binding of the short isoform of AATYK1 to p35 and its phosphorylation by Cdk5 in vitro and in cultured cells [15]; however, the interaction of AATYK1A, the major isoform in neurons, with Cdk5/p35 has not been examined. Furthermore, the phosphorylation site and the role of phosphorylation have not been addressed.…”

Section: Introductionmentioning

confidence: 97%

Phosphorylation of AATYK1 by Cdk5 Suppresses Its Tyrosine Phosphorylation

et al. 2010

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Apoptosis-associated tyrosine kinase 1 (AATYK1), a novel serine/threonine kinase that is highly expressed in the brain, is involved in neurite extension and apoptosis of cerebellar granule neurons; however, its precise function remains unknown. In this study, we investigated the interaction of AATYK1A with Cyclin-dependent kinase 5 (Cdk5)/p35, a proline-directed protein kinase that is predominantly expressed in neurons. AATYK1A bound to the p35 activation subunit of Cdk5 in cultured cells and in mouse brains and colocalized with p35 on endosomes in COS-7 cells. AATYK1A was phosphorylated at Ser34 by Cdk5/p35 in vitro, in cultured neurons and in mouse brain. In PC12D cells, Ser34 phosphorylation increased after treatment with nerve growth factor and phosphorylated AATYK1A accumulated in growth cones of PC12D cells. Ser34 phosphorylation suppressed the tyrosine phosphorylation of AATYK1A by Src family kinases. These results suggest a possibility that AATYK1A plays a role in early to recycling endosomes and its function is regulated by phosphorylation with Cdk5 or Src-family kinases.

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“…This observation was confirmed through the use of Ca 2+ channel antagonists and activators which resulted in hyper- and hypo-phosphorylation of AATYK, respectively (126). Another yeast-2-hybrid screen of a human brain cDNA library with the Cdk5 activator p35 as a bait identified a fragment of AATYK, suggesting that the tyrosine kinase might be a novel Cdk5/p35 binding and substrate protein (122). Knockout AATYK2 mice have been generated and although the testicular somatic cells appear normal, the germ cells fail to differentiate into elongated spermatids resulting in infertile males (139).…”

Section: Molecular Characteristics Of Spak and Osr1mentioning

confidence: 99%

Molecular Physiology of SPAK and OSR1: Two Ste20-Related Protein Kinases Regulating Ion Transport

Gagnon

Delpire

2012

Physiological Reviews

119

108

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SPAK (Ste20-related proline alanine rich kinase) and OSR1 (oxidative stress responsive kinase) are members of the germinal center kinase VI sub-family of the mammalian Ste20 (Sterile20)-related protein kinase family. Although there are 30 enzymes in this protein kinase family, their conservation across the fungi, plant and animal kingdom confirms their evolutionary importance. Already, a large volume of work has accumulated on the tissue distribution, binding partners, signaling cascades, and physiological roles of mammalian SPAK and OSR1 in multiple organ systems. After reviewing this basic information, we will examine newer studies that demonstrate the pathophysiological consequences to SPAK and/or OSR1 disruption, discuss the development and analysis of genetically-engineered mouse models, and address the possible role these serine/threonine kinases might have in cancer proliferation and migration.

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Apoptosis-associated tyrosine kinase is a Cdk5 activator p35 binding protein

Cited by 25 publications

References 26 publications

miR‐338‐3p suppresses neuroblastoma proliferation, invasion and migration through targeting PREX2a

miR‐338‐3p suppresses neuroblastoma proliferation, invasion and migration through targeting PREX2a

Phosphorylation of AATYK1 by Cdk5 Suppresses Its Tyrosine Phosphorylation

Molecular Physiology of SPAK and OSR1: Two Ste20-Related Protein Kinases Regulating Ion Transport

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