Induction of neurite outgrowth in PC12 cells by the bacterial nucleoside N6-methyldeoxyadenosine is mediated through adenosine A2a receptors and via cAMP and MAPK signaling pathways

Charles, Marie-Pierre; Adamski, Danièle; Kholler, Blandine; Pelletier, Laurent; Berger, François; Wion, Didier

doi:10.1016/s0006-291x(03)00666-1

Cited by 32 publications

(33 citation statements)

References 27 publications

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“…Bacterial N 6 -methyldeoxy adenosine, a newly found active adenosine derivative, might be useful for future study, because it induced neurite outgrowth in PC12 cells through adenosine A 2 A receptor. 38) Although the mechanisms of neuritogenesis were found to be different between AMP N 1 -oxide and NGF, many reports have shown interactions between the A 2 A receptor-mediated signal and the intracellular NGF signal. For instance, the A 2 A receptor-mediated signal played a supportive role in rescuing impaired NGFinduced neurite outgrowth, 39) transactivated TrkA receptor, a high affinity receptor of NGF, 40) and caused complicated negative or positive effects on the NGFinduced phosphorylation of mitogen-activated protein kinase phosphorylation 41) in PC12 cells.…”

Section: Discussionmentioning

confidence: 99%

Identification of AMPN₁-Oxide in Royal Jelly as a Component Neurotrophic toward Cultured Rat Pheochromocytoma PC12 Cells

Hattori

Nishimura

Mishima

et al. 2006

Bioscience, Biotechnology, and Biochemistry

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Section: Discussionmentioning

confidence: 99%

Identification of AMPN₁-Oxide in Royal Jelly as a Component Neurotrophic toward Cultured Rat Pheochromocytoma PC12 Cells

Hattori

Nishimura

Mishima

et al. 2006

Bioscience, Biotechnology, and Biochemistry

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“…Another important cAMP effector, Epac (Bos, 2003), has recently been shown to convert a PKA-mediated proliferative signal into a differentiation signal in PC-12 cells (Kiermayer et al, 2005). In addition, activation of the A 2A -R during hypoxia or by a prokaryotic nucleoside has been shown to induce neurite outgrowth via a cAMP-dependent pathway (Charles et al, 2003;O'Driscoll and Gorman, 2005). Although TRAX seems to play the major role in mediating the rescue effect of A 2A -R on p53 blockage ( Fig.…”

Section: Trax Mediates a 2a -R Suppression Of Proliferation 463mentioning

confidence: 96%

“…The A 2A adenosine receptor (A 2A -R) belongs to the G protein-coupled receptor (GPCR) family and is involved in regulating neuronal plasticity and development (Weaver, 1993;Ribeiro, 1999;Cheng et al, 2002). We and others have previously demonstrated that in PC-12 cells, stimulation of the A 2A -R activates at least two major cellular signaling cascades: adenylyl cyclase/cAMP/protein kinase A (PKA) and the protein kinase C (PKC)-mediated pathways (Sobreviela et al, 1994;Chang et al, 1997;Huang et al, 2001;Charles et al, 2003). In addition, A 2A -R stimulation rescues the ability of PC-12 cells to proceed with NGF-evoked neurite outgrowth when the MAPK cascade is impaired (Cheng et al, 2002).…”

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confidence: 99%

Rescue of p53 Blockage by the A_2AAdenosine Receptor via a Novel Interacting Protein, Translin-Associated Protein X

Sun¹,

Cheng²,

Chou³

et al. 2006

Mol Pharmacol

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Blockage of the p53 tumor suppressor has been found to impair nerve growth factor (NGF)-induced neurite outgrowth in PC-12 cells. We report herein that such impairment could be rescued by stimulation of the A 2A adenosine receptor (A 2A -R), a G protein-coupled receptor implicated in neuronal plasticity. The A 2A -R-mediated rescue occurred in the presence of protein kinase C (PKC) inhibitors or protein kinase A (PKA) inhibitors and in a PKA-deficient PC-12 variant. Thus, neither PKA nor PKC was involved. In contrast, expression of a truncated A 2A -R mutant harboring the seventh transmembrane domain and its C terminus reduced the rescue effect of A 2A -R. Using the cytoplasmic tail of the A 2A -R as bait, a novel-A 2A -R-interacting protein [translin-associated protein X (TRAX)] was identified in a yeast two-hybrid screen. The authenticity of this interaction was verified by pull-down experiments, coimmunoprecipitation, and colocalization of these two molecules in the brain. It is noteworthy that reduction of TRAX using an antisense construct suppressed the rescue effect of A 2A -R, whereas overexpression of TRAX alone caused the same rescue effect as did A 2A -R activation. Results of [ 3 H]thymidine and bromodeoxyuridine incorporation suggested that A 2A -R stimulation inhibited cell proliferation in a TRAX-dependent manner. Because the antimitotic activity is crucial for NGF function, the A 2A -R might exert its rescue effect through a TRAX-mediated antiproliferative signal. This antimitotic activity of the A 2A -R also enables a mitogenic factor (epidermal growth factor) to induce neurite outgrowth. We demonstrate that the A 2A -R modulates the differentiation ability of trophic factors through a novel interacting protein, TRAX.

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“…Later, it was published by the same group that methylation of Arg 31 of STAT1 is necessary for its dephosphorylation by the phosphatase TcPTP (5). Similarly, for STAT6, arginine methylation has been described to be important for STAT6 function (6).…”

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confidence: 99%

Are STATS Arginine-methylated?

Komyod

Bauer

Heinrich

et al. 2005

Journal of Biological Chemistry

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Transcription factors of the STAT (signal transducer and activator of transcription) family are important in signal transduction of cytokines. They are subject to post-translational modification by phosphorylation on tyrosine and serine residues. Recent evidence suggested that STATs are methylated on a conserved arginine residue within the N-terminal region. STAT arginine methylation has been described to be important for STAT function and loss of arginine methylation was discussed to be involved in interferon resistance of cancer cells. Here we provide several independent lines of evidence indicating that the issue of arginine methylation of STATs has to be reassessed. First, we show that treatment of melanoma and fibrosarcoma cells with inhibitors used to suppress methylation (N-methyl-2-deoxyadenosine, adenosine, DL-homocysteine) had profound and rapid effects on phosphorylation of STAT1 and STAT3 but also on p38 and Erk signaling cascades which are known to cross-talk with the Jak/STAT pathway. Second, we show that anti-methylarginine antibodies did not precipitate specifically STAT1 or STAT3. Third, we show that mutation of Arg 31 to Lys led to destabilization of STAT1 and STAT3, implicating an important structural role of Arg 31 . Finally, purified catalytically active protein arginine methyltransferases (PRMT1, -2, -3, -4, and -6) did not methylate STAT proteins, and cotransfection with PRMT1 did not affect STAT1-controlled reporter gene activity. Taken together, our data suggest the absence of arginine methylation of STAT1 and STAT3.Signal transducers and activators of transcription (STAT) 1 proteins comprise a family of transcription factors (molecular mass: ϳ90 kDa), which are specifically activated to regulate gene transcription when cells encounter cytokines and growth factors. Subsequent to receptor binding, the STAT proteins are phosphorylated on a single tyrosine residue (Tyr 701 in STAT1 and Tyr 705 in STAT3). The phosphorylated STATs dissociate from the receptors, form active dimers through interactions of their SH2 domains, and translocate to the nucleus to induce gene transcription. In addition to tyrosine phosphorylation, STATs 1, 3, and 5 also require phosphorylation on a serine residue in the C-terminal region to achieve maximal transactivation potential (1-3).Previously, a model has been proposed suggesting that STAT1 methylation on arginine at position 31 is functionally necessary since it suppresses the interaction with the negative regulatory protein PIAS (4). Later, it was published by the same group that methylation of Arg 31 of STAT1 is necessary for its dephosphorylation by the phosphatase TcPTP (5). Similarly, for STAT6, arginine methylation has been described to be important for STAT6 function (6). Mostly, these studies have made use of antibodies directed against methylarginine, STAT mutants, and inhibitors of methylation, methylthioadenosine (MTA) (4) or N-methyl-2-deoxyadenosine (MDA), in the presence of adenosine and DL-homocysteine (5-7). In addition, STAT3 has been shown to ...

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Induction of neurite outgrowth in PC12 cells by the bacterial nucleoside N6-methyldeoxyadenosine is mediated through adenosine A2a receptors and via cAMP and MAPK signaling pathways

Cited by 32 publications

References 27 publications

Identification of AMPN₁-Oxide in Royal Jelly as a Component Neurotrophic toward Cultured Rat Pheochromocytoma PC12 Cells

Identification of AMPN₁-Oxide in Royal Jelly as a Component Neurotrophic toward Cultured Rat Pheochromocytoma PC12 Cells

Rescue of p53 Blockage by the A_2AAdenosine Receptor via a Novel Interacting Protein, Translin-Associated Protein X

Are STATS Arginine-methylated?

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Induction of neurite outgrowth in PC12 cells by the bacterial nucleoside N6-methyldeoxyadenosine is mediated through adenosine A2a receptors and via cAMP and MAPK signaling pathways

Cited by 32 publications

References 27 publications

Identification of AMPN1-Oxide in Royal Jelly as a Component Neurotrophic toward Cultured Rat Pheochromocytoma PC12 Cells

Identification of AMPN1-Oxide in Royal Jelly as a Component Neurotrophic toward Cultured Rat Pheochromocytoma PC12 Cells

Rescue of p53 Blockage by the A2AAdenosine Receptor via a Novel Interacting Protein, Translin-Associated Protein X

Are STATS Arginine-methylated?

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Identification of AMPN₁-Oxide in Royal Jelly as a Component Neurotrophic toward Cultured Rat Pheochromocytoma PC12 Cells

Identification of AMPN₁-Oxide in Royal Jelly as a Component Neurotrophic toward Cultured Rat Pheochromocytoma PC12 Cells

Rescue of p53 Blockage by the A_2AAdenosine Receptor via a Novel Interacting Protein, Translin-Associated Protein X