scholarly journals Nocturnal Activation of Aurora C in Rat Pineal Gland: Its Role in the Norepinephrine-Induced Phosphorylation of Histone H3 and Gene Expression

Endocrinology ◽  
2008 ◽  
Vol 150 (5) ◽  
pp. 2334-2341 ◽  
Author(s):  
D. M. Price ◽  
R. Kanyo ◽  
N. Steinberg ◽  
C. L. Chik ◽  
A. K. Ho
Keyword(s):  
Protein Kinase ◽  
Pineal Gland ◽  
Protein Kinase A ◽  
Histone H3 ◽  
Time Profile ◽  
Mitotic Kinase ◽  
H3 Phosphorylation ◽  
Histone H3 Phosphorylation ◽  
Rat Pineal Gland ◽  
Kinase A

We have shown previously that Ser10 phosphorylation of histone H3 occurs in rat pinealocytes after stimulation with norepinephrine (NE) and that histone modifications such as acetylation appear to play an important role in pineal gene transcription. Here we report the nocturnal phosphorylation of a Ser10 histone H3 kinase, Aurora C, in the rat pineal gland. The time profile of this phosphorylation parallels the increase in the level of phospho-Ser10 histone H3. Studies with cultured pinealocytes indicate that Aurora C phosphorylation is induced by NE and this induction can be blocked by cotreatment with propranolol or KT5720, a protein kinase A inhibitor. Moreover, only treatment with dibutyryl cAMP, but not other kinase activators, mimics the effect of NE on Aurora C phosphorylation. These results indicate that Aurora C is phosphorylated primarily by a β-adrenergic/protein kinase A-mediated mechanism. Treatment with an Aurora C inhibitor reduces the NE-induced histone H3 phosphorylation and suppresses the NE-stimulated induction of arylalkylamine N-acetyltransferase (AA-NAT), the rhythm-controlling enzyme of melatonin synthesis, and melatonin production. The effects of Aurora C inhibitors on adrenergic-induced genes in rat pinealocytes are gene specific: inhibitory for Aa-nat and inducible cAMP repressor but stimulatory for c-fos. Together our results support a role for the NE-stimulated phosphorylation of Aurora C and the subsequent remodeling of chromatin in NE-stimulated Aa-nat transcription. This phenomenon suggests that activation of this mitotic kinase can be induced by extracellular signals to participate in the transcriptional induction of a subset of genes in the rat pineal gland.

scholarly journals Adrenergic Regulation and Diurnal Rhythm of p38 Mitogen-Activated Protein Kinase Phosphorylation in the Rat Pineal Gland

Endocrinology ◽  
2004 ◽  
Vol 145 (11) ◽  
pp. 5194-5201 ◽  
Author(s):  
C. L. Chik ◽  
M. Mackova ◽  
D. Price ◽  
A. K. Ho
Keyword(s):  
Protein Kinase ◽  
Pineal Gland ◽  
Protein Kinase A ◽  
Time Course ◽  
Kinase Inhibitor ◽  
Mitogen Activated Protein Kinase ◽  
Mitogen Activated Protein ◽  
Adrenergic Blocker ◽  
Rat Pineal Gland ◽  
Kinase A

Abstract In this study, we investigated adrenergic and photoneural regulation of p38MAPK phosphorylation in the rat pineal gland. Norepinephrine (NE), the endogenous neurotransmitter, dose-dependently increased the levels of phosphorylated MAPK kinase 3/6 (MKK3/6) and p38MAPK in rat pinealocytes. Time-course studies showed a gradual increase in MKK3/6 and p38MAPK phosphorylation that peaked between 1 and 2 h and persisted for 4 h post NE stimulation. In cells treated with NE for 2 and 4 h, the inclusion of prazosin or propranolol reduced NE-induced MKK3/6 and p38MAPK phosphorylation, indicating involvement of both α- and β-adrenergic receptors for the sustained response. Whereas treatment with dibutyryl cAMP or ionomycin mimicked the NE-induced MKK3/6 and p38MAPK phosphorylation, neither dibutyryl cGMP nor 4β-phorbol 12-myristate 13-acetate had an effect. The NE-induced increase in MKK3/6 and p38MAPK phosphorylation was blocked by KT5720 (a protein kinase A inhibitor) and KN93 (a Ca2+/calmodulin-dependent kinase inhibitor), but not by KT5823 (a protein kinase G inhibitor) or calphostin C (a protein kinase C inhibitor). In animals housed under a lighting regimen with 12 h of light, MKK3/6 and p38MAPK phosphorylation increased in the rat pineal gland at zeitgeber time 18. The nocturnal increase in p38MAPK phosphorylation was blocked by exposing the animal to constant light and reduced by treatment with propranolol, a β-adrenergic blocker. Together, our results indicate that activation of p38MAPK is under photoneural control in the rat pineal gland and that protein kinase A and intracellular Ca2+ signaling pathways are involved in NE regulation of p38MAPK.

scholarly journals Histone H3 Phosphorylation in the Rat Pineal Gland: Adrenergic Regulation and Diurnal Variation

Endocrinology ◽  
2007 ◽  
Vol 148 (4) ◽  
pp. 1465-1472 ◽  
Author(s):  
C. L. Chik ◽  
T. G. Arnason ◽  
W. G. Dukewich ◽  
D. M. Price ◽  
A. Ranger ◽  
...  
Keyword(s):  
Pineal Gland ◽  
Diurnal Variation ◽  
Histone H3 ◽  
Adrenergic Regulation ◽  
H3 Phosphorylation ◽  
Histone H3 Phosphorylation ◽  
Rat Pineal Gland

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

2002 ◽  
Vol 293 (2) ◽  
pp. 753-758 ◽  
Author(s):  
Yoshihiro Hashimoto ◽  
Hidetoshi Akita ◽  
Mitsunobu Hibino ◽  
Kenjiro Kohri ◽  
Makoto Nakanishi
Keyword(s):  
Protein Kinase ◽  
Protein Kinase A ◽  
Histone H3 ◽  
Human Homolog ◽  
Identification And Characterization ◽  
Kinase A

scholarly journals Mitogen-activated protein kinase phosphatase 2 regulates histone H3 phosphorylation via interaction with vaccinia-related kinase 1

2013 ◽  
Vol 24 (3) ◽  
pp. 373-384 ◽  
Author(s):  
Min-Woo Jeong ◽  
Tae-Hong Kang ◽  
Wanil Kim ◽  
Yoon Ha Choi ◽  
Kyong-Tai Kim
Keyword(s):  
Protein Kinase ◽  
Histone H3 ◽  
Negative Regulator ◽  
Mitogen Activated Protein Kinase ◽  
H3 Phosphorylation ◽  
Dual Specificity ◽  
Selective Interaction ◽  
M Phase ◽  
Mitogen Activated Protein ◽  
Histone H3 Phosphorylation

Mitogen-activated protein kinase phosphatase 2 (MKP2) is a member of the dual-specificity MKPs that regulate MAP kinase signaling. However, MKP2 functions are still largely unknown. In this study, we showed that MKP2 could regulate histone H3 phosphorylation under oxidative stress conditions. We found that MKP2 inhibited histone H3 phosphorylation by suppressing vaccinia-related kinase 1 (VRK1) activity. Moreover, this regulation was dependent on the selective interaction with VRK1, regardless of its phosphatase activity. The interaction between MKP2 and VRK1 mainly occurred in the chromatin, where histones are abundant. We also observed that the protein level of MKP2 and its interaction with histone H3 increased from G1 to M phase during the cell cycle, which is similar to the VRK1 profile. Furthermore, MKP2 specifically regulated the VRK1-mediated histone H3 phosphorylation at M phase. Taken together, these data suggest a novel function of MKP2 as a negative regulator of VRK1-mediated histone H3 phosphorylation.

scholarly journals Protein Kinase A-mediated Serine 35 Phosphorylation Dissociates Histone H1.4 from Mitotic Chromosome

2011 ◽  
Vol 286 (41) ◽  
pp. 35843-35851 ◽  
Author(s):  
Chi-Shuen Chu ◽  
Pang-Hung Hsu ◽  
Pei-Wen Lo ◽  
Elisabeth Scheer ◽  
Laszlo Tora ◽  
...  
Keyword(s):  
Protein Kinase ◽  
Protein Kinase A ◽  
Cell Cycle Progression ◽  
Mass Spectrometry Analysis ◽  
Cycle Progression ◽  
Spectrometry Analysis ◽  
H3 Phosphorylation ◽  
Substitution Mutant ◽  
Kinase A ◽  
Mitotic Chromatin

Global histone H1 phosphorylation correlates with cell cycle progression. However, the function of site-specific H1 variant phosphorylation remains unclear. Our mass spectrometry analysis revealed a novel N-terminal phosphorylation of the major H1 variant H1.4 at serine 35 (H1.4S35ph), which accumulates at mitosis immediately after H3 phosphorylation at serine 10. Protein kinase A (PKA) was found to be a kinase for H1.4S35. Importantly, Ser-35-phosphorylated H1.4 dissociates from mitotic chromatin. Moreover, H1.4S35A substitution mutant cannot efficiently rescue the mitotic defect following H1.4 depletion, and inhibition of PKA activity increases the mitotic chromatin compaction depending on H1.4. Our results not only indicate that PKA-mediated H1.4S35 phosphorylation dissociates H1.4 from mitotic chromatin but also suggest that this phosphorylation is necessary for specific mitotic functions.

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