Identification and characterization of Nek6 protein kinase, a potential human homolog of NIMA histone H3 kinase

Hashimoto, Yoshihiro; Akita, Hidetoshi; Hibino, Mitsunobu; Kohri, Kenjiro; Nakanishi, Makoto

doi:10.1016/s0006-291x(02)00297-8

Cited by 24 publications

(15 citation statements)

References 33 publications

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“…The PHOSIDA database also identifies an additional phosphorylation site at Ser112 that should be present only in the interferon-inducible full-length ADAR1 isoform. The main kinase involved in the phosphorylation of ADAR1 is likely never in mitosis gene A (NIMA)-related kinase 6 (NEK6), which is a serine/threonine protein kinase that is implicated in cell cycle regulation [145,146]. When human ADAR2 was analyzed with PhosphoSitePlus® [129,134,136], only two phosphorylation sites, Ser26 and Thr740, were found; Ser26 is located in the N-terminal, while Thr740 is located in the C-terminal domain, and both are not present in the ADAR2 isoforms ADAR2c and ADAR2d (Table 1).…”

Section: Phosphorylationmentioning

confidence: 99%

Activity Regulation of Adenosine Deaminases Acting on RNA (ADARs)

2011

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Adenosine deaminases acting on RNA (ADARs) are the enzymes that are responsible for the A to I RNA editing process in mammals, which is an important mechanism that increases molecular diversity. A to I RNA editing consists of an enzymatic conversion of specific adenosine in pre-mRNA, leading to alteration of the properties of both the RNA itself and the translated protein. Currently, the importance of this phenomenon is increasingly recognized as it affects a diverse set of cellular pathways. ADAR function within the cell, especially in the neurons, is to diversify the features of a limited set of unique transcripts, mostly neurotransmitter receptors; however, a growing set of target is going to be discovered, increasing the importance of the RNA editing event in the proper physiology of the cell. Despite the functional relevance of these enzymes, there is a gap of knowledge in the mechanisms that regulate ADAR activity and consequently about the modulation of RNA editing process. This review summarizes ongoing investigations of ADAR regulation at the transcriptional, post-transcriptional and post-translational level and addresses new hypothetical mechanisms that are capable of modulating ADAR activity, including subcellular localization, dimerization and interaction with trans-acting factors.

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Section: Phosphorylationmentioning

confidence: 99%

Activity Regulation of Adenosine Deaminases Acting on RNA (ADARs)

2011

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“…In addition, NEK6 is phosphorylated and activated during M phase and inhibition of the kinase arrests cells in M phase and triggers apoptosis (105). Furthermore, NEK6 functions as a mitotic histone kinase that regulates chromatin condensation in mammalian cells (50). Thus the finding that NEK6 functions as a PDK2 is somewhat surprising, as phosphorylation of the AGC family kinases at the HM site has not been shown to be cell cycle dependent.…”

Section: Phosphorylation Of the Hm Site By A Heterologous Kinase(s)?mentioning

confidence: 99%

PDK2: the missing piece in the receptor tyrosine kinase signaling pathway puzzle

Dong

Liu

2005

American Journal of Physiology-Endocrinology and Metabolism

127

113

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Activation of members of the protein kinase AGC (cAMP dependent, cGMP dependent, and protein kinase C) family is regulated primarily by phosphorylation at two sites: a conserved threonine residue in the activation loop and a serine/threonine residue in a hydrophobic motif (HM) near the COOH terminus. Although phosphorylation of these kinases in the activation loop has been found to be mediated by phosphoinositide-dependent protein kinase-1 (PDK1), the kinase(s) that catalyzes AGC kinase phosphorylation in the HM remains uncharacterized. So far, at least 10 kinases have been suggested to function as an HM kinase or the so-called “PDK2,” including mitogen-activated protein (MAP) kinase-activated protein kinase-2 (MK2), integrin-linked kinase (ILK), p38 MAP kinase, protein kinase Cα (PKCα), PKCβ, the NIMA-related kinase-6 (NEK6), the mammalian target of rapamycin (mTOR), the double-stranded DNA-dependent protein kinase (DNK-PK), and the ataxia telangiectasia mutated (ATM) gene product. However, whether any or all of these kinases act as a physiological HM kinase remains to be established. Nonetheless, available data suggest that multiple systems may be used in cells to regulate the activation of the AGC family kinases. It is possible that, unlike activation loop phosphorylation, phosphorylation of the HM site in the different AGC family kinases is mediated by distinct kinases. In addition, phosphorylation of the AGC family kinase at the HM site could be cell type, signaling pathway, and substrate specific. Identification and characterization of the bonafide HM kinase(s) will be essential to verify these hypotheses.

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“…NIMA (Never In Mitosis, gene A) kinase is required for G 2 /M progression (Osmani et al, 1991) and has been shown to activate chromatin condensation and promote entry into mitosis (O'Connell et al, 1994;Lu and Hunter, 1995;Osmani and Ye, 1996). The human orthologs of NIMA, the Nek (NIMA Related Kinase) kinases, are a family of serine/threonine kinases consisting of the members: Nek1 (Letwin et al, 1992), Nek2 (Schultz et al, 1994;Fry et al, 1995), Nek3 (Tanaka and Nigg, 1999), Nek4/STK2 (Levedakou et al, 1994), Nek6 (Li et al, 1999;Hashimoto et al, 2002;Minoguchi et al, 2003), Nek7 (Kimura and Okano, 2001;Minoguchi et al, 2003), Nek9/Nercc1 (Holland et al, 2002;Roig et al, 2002), Nek11 (Noguchi et al, 2002), as well as three predicted, but unpublished Neks (Manning et al, 2002). Nek9/ Nercc1 was initially designated as Nek8 and Nercc1, but has subsequently been renamed within Genbank as Nek9/Nercc1.…”

Section: Introductionmentioning

confidence: 99%