Agonist-specific Transactivation of Phosphoinositide 3-Kinase Signaling Pathway Mediated by the Dopamine D2 Receptor

Nair, Venugopalan D.; Sealfon, Stuart C.

doi:10.1074/jbc.m303364200

Cited by 87 publications

(90 citation statements)

References 60 publications

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“…Unlike in HEK293/A 1 R cells, no EGFR phosphorylation at the residue Tyr1068 was detected following A 1 R stimulation in primary cortical neurons ( Figure 6C). Src-kinase has been reported to be involved in EGFR phosphorylation and to form a multiprotein complex with GPCR and EGFR [14] . The inhibition of either Src or EGFR kinase impairs the ability of CPA to induce the phosphorylation of EGFR and Akt in cortical neurons, indicating that the activation of both proteins is required for this cascade.…”

Section: Discussionmentioning

confidence: 99%

“…The indicated drugs were also included in the OGD solution during the OGD period. At the end of the OGD period (4 h), cultures were returned to the conditioned medium for another 12 h. Cell viability was assessed by metabolize 3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyltetrazdium bromide (MTT), as described previously [14] . 12 h after OGD treatment, the MTT solution (0.5 mg/mL) was added to each well, and cells were maintained in growth medium for 4 h. After solubilization with DMSO, the absorbance of the formazan dye was measured using a microplate reader (NovoStar, BMG) at 595 nm.…”

Section: Methodsmentioning

confidence: 99%

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Adenosine A1 receptor-mediated transactivation of the EGF receptor produces a neuroprotective effect on cortical neurons in vitro

et al. 2009

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Aim: To understand the mechanism of the transactivation of the epidermal growth factor receptor (EGFR) mediated by the adenosine A 1 receptor (A 1 R). Methods: Primary cultured rat cortical neurons subjected to oxygen-glucose deprivation (OGD) and HEK293/A 1 R cells were treated with the A 1 R-specific agonist N 6 -cyclopentyladenosine (CPA). Phospho-EGFR, Akt, and ERK1/2 were observed by Western blot. An interaction between EGFR and A 1 R was detected using immunoprecipitation and immunocytochemistry. Results: The A 1 R agonist CPA causes protein kinase B (Akt) activation and protects primary cortical neurons from oxygen-glucose deprivation (OGD) insult. A 1 R and EGFR co-localize in the membranes of neurons and form an immunocomplex. A 1 R stimulation induces significant EGFR phosphorylation via a PI3K and Src kinase signaling pathway; this stimulation provides a neuroprotective effect in cortical neurons. CPA leads to sustained phosphorylation of extracellularly regulated kinases 1 and 2 (ERK1/2) in cortical neurons, but only to transient phosphorylation in HEK 293/A 1 R cells. The response to the A 1 R agonist is mediated primarily through EGFR transactivation that is dependent on pertussis toxin (PTX)-sensitive G i protein and metalloproteases in HEK 293/A 1 R. Conclusion: A 1 R-mediated EGFR transactivation confers a neuroprotective effect in primary cortical neurons. PI3 kinase and Src kinase play pivotal roles in this response.

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Section: Discussionmentioning

confidence: 99%

Section: Methodsmentioning

confidence: 99%

Adenosine A1 receptor-mediated transactivation of the EGF receptor produces a neuroprotective effect on cortical neurons in vitro

et al. 2009

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“…The riboprobes were purified on atlas nucleospin columns. The cells grown on cover slips were fixed and permeabilized as described previously (31,32). After prehybridization in 5ϫ SSC, 50% formamide, and 1 mg/ml tRNA at room temperature for 30 min, the denatured probe was added to the prehybridization buffer.…”

Section: Methodsmentioning

confidence: 99%

“…The cells were fixed and permeabilized as described previously (31,32), and immunocytochemical staining for phospho-ERK, phospho-p53, or active caspase-3 was carried out. Anti-phospho-ERK (1:400), anti-phospho-p53 (1:500), or active caspase-3 antibody (1:200) was added and incubated overnight at 4°C.…”

Section: Methodsmentioning

confidence: 99%

“…We have reported recently that H 2 O 2 induces apoptosis in PC-12-D 2 R cells and in the nigral dopaminergic neuronal cell line SN4741 in a concentration-dependent manner (31,32). These observations suggest that when exposed to a level of oxidative stress that can induce apoptosis in a portion of cells, each individual cell must proceed through a decision-making process that ultimately results either in its survival or its death.…”

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Early Single Cell Bifurcation of Pro- and Antiapoptotic States during Oxidative Stress

Nair

Yuen

Olanow

et al. 2004

Journal of Biological Chemistry

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IL‐1β induces MMP‐9 expression via a Ca²⁺‐dependent CaMKII/JNK/c‐JUN cascade in rat brain astrocytes

Hsieh

Sun

et al. 2009

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Interleukin (IL)-1beta has been shown to induce matrix metalloproteinase (MMP)-9 expression through mitogen-activated protein kinases, including JNK, in rat brain astrocyte-1 (RBA-1) cells. However, little is known about whether JNK activated by Ca(2+)-dependent CaMKII is associated with MMP-9 expression induced by IL-1beta. Here, we report that the Ca(2+)/CaMKII/JNK/c-Jun participates in the MMP-9 expression induced by IL-1beta. Zymographic, Western blotting, and RT-PCR analyses showed that IL-1beta-induced expression of MMP-9 mRNA and protein was attenuated by Ca(2+) chelator (BAPTA), and the inhibitors of ER Ca(2+)-ATPase (thapsigargin), CaMKII (KN-62), and JNK1/2 (SP600125). IL-1beta also stimulated phosphorylation of CaMKII and JNK1/2, and increase in intracellular Ca(2+) ([Ca(2+)](i)), which were inhibited by pretreatment with BAPTA, thapsigargin (TG), KN-62, or SP600125. Furthermore, the upregulation of MMP-9 protein was blocked by transfection with c-Jun or CaMKII short hairpin RNA (shRNA). We further confirmed that IL-1beta stimulated c-Jun associated with AP-1-binding sites within MMP-9 promoter (-87 to -80 bp and -511 to -497 bp) by immunoprecipitation and chromatin immunoprecipitation (ChIP)-PCR assays. The activation and recruitment of c-Jun to MMP-9 promoter were inhibited by pretreatment with BAPTA, TG, KN-62, or SP600125. Moreover, IL-1beta-induced MMP-9 gene transcription by AP-1 was confirmed by transfection with a MMP-9 promoter-luciferase reporter plasmid with a distal AP-1-binding site (-511 to -497 bp) adjacent to an Ets-binding site-mutation (mt-AP1/Ets-MMP-9). These results demonstrated that in RBA-1 cells, JNK/c-Jun activation was mediated through a Ca(2+)-dependent CaMKII pathway that promoted transcription factor c-Jun/AP-1 recruitment and eventually led to increase in MMP-9 expression by IL-1beta.

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Agonist-specific Transactivation of Phosphoinositide 3-Kinase Signaling Pathway Mediated by the Dopamine D2 Receptor

Cited by 87 publications

References 60 publications

Adenosine A1 receptor-mediated transactivation of the EGF receptor produces a neuroprotective effect on cortical neurons in vitro

Adenosine A1 receptor-mediated transactivation of the EGF receptor produces a neuroprotective effect on cortical neurons in vitro

Early Single Cell Bifurcation of Pro- and Antiapoptotic States during Oxidative Stress

IL‐1β induces MMP‐9 expression via a Ca²⁺‐dependent CaMKII/JNK/c‐JUN cascade in rat brain astrocytes

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Agonist-specific Transactivation of Phosphoinositide 3-Kinase Signaling Pathway Mediated by the Dopamine D2 Receptor

Cited by 87 publications

References 60 publications

Adenosine A1 receptor-mediated transactivation of the EGF receptor produces a neuroprotective effect on cortical neurons in vitro

Adenosine A1 receptor-mediated transactivation of the EGF receptor produces a neuroprotective effect on cortical neurons in vitro

Early Single Cell Bifurcation of Pro- and Antiapoptotic States during Oxidative Stress

IL‐1β induces MMP‐9 expression via a Ca2+‐dependent CaMKII/JNK/c‐JUN cascade in rat brain astrocytes

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IL‐1β induces MMP‐9 expression via a Ca²⁺‐dependent CaMKII/JNK/c‐JUN cascade in rat brain astrocytes