Activation of Microtubule‐Associated Protein Kinase (Erk) and p70 S6 Kinase by D<sub>2</sub> Dopamine Receptors

Welsh, Gavin I.; Hall, David A.; Warnes, Andrew; Strange, Philip G.; Proud, Christopher G.

doi:10.1046/j.1471-4159.1998.70052139.x

Cited by 74 publications

(61 citation statements)

References 42 publications

(54 reference statements)

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“…MAPK activation by D2R was reported in some cell lines stably expressing D2R (Luo et al 1998;Welsh et al 1998;Choi et al 1999;Oak et al 2001) and in cortical slice culture (Yan et al 1999). Consistent with previous reports, D2R stimulation clearly activated ERK in NGD2LR (Fig.…”

Section: Discussionsupporting

confidence: 90%

“…Furthermore, D2R stimulation activates several protein kinases. It has been recently reported that D2R stimulation activates mitogen-activated protein kinases (MAPKs), namely, extracellular signal-regulated kinase (ERK) and c-Jun NH 2 -terminal kinase (JNK), in several cell lines expressing D2R (Luo et al 1998;Welsh et al 1998;Choi et al 1999;Oak et al 2001) and in rat brain slices culture (Yan et al 1999). Several signalling pathways through D2R are involved in MAPK activation.…”

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confidence: 99%

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Differential regulation of NF‐κB, SRE and CRE by dopamine D1 and D2 receptors in transfected NG108‐15 cells

Takeuchi

Fukunaga

2003

Journal of Neurochemistry

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To investigate transcriptional regulation by dopamine receptors, we established NG108-15 cells stably expressing D1R, D2LR and D2SR (NGD1R, NGD2LR and NGD2SR) and evaluated the effects of these receptors on NF-jB, SRE and CRE activity using luciferase reporter constructs. Stimulation with quinpirole, a selective D2R agonist, increased NF-jB and SRE activity but decreased CRE activity in both NGD2R cell lines. By contrast, stimulation with SKF 38393, a selective D1R agonist, decreased NF-jB and SRE activity but increased CRE activity in NGD1R cells. Stimulation with forskolin and overexpression of constitutively active PKA suppressed NF-jB activity, likely due to D1R stimulation. D2R stimulation activated ERK, and treatment with U1026, a selective MEK inhibitor, eliminated D2R-induced NF-jB activation. D2R stimulation also activated the neural cell adhesion molecule (NCAM) promoter, which includes a potential NF-jB site. Furthermore, by transfecting constitutively active CaM KII and MEKK, and dominant negative p38 MAPK, we show that the NCAM promoter is positively regulated by CaM KII but negatively regulated by p38 MAPK. These results indicate that D2R-induced NF-jB activation through ERK may be involved in activation of the NCAM promoter, and additionally that other protein kinases such as CaM KII and p38 MAPK also regulate NCAM expression.

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Section: Discussionsupporting

confidence: 90%

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confidence: 99%

Differential regulation of NF‐κB, SRE and CRE by dopamine D1 and D2 receptors in transfected NG108‐15 cells

Takeuchi

Fukunaga

2003

Journal of Neurochemistry

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“…Serotonin (5-HT) addition to Aplysia neurons or Chinese hamster ovary (CHO) cells expressing the 5-HT1B receptor increases phosphorylation of S6K1 in a rapamycin-dependent manner (113,114). Dopamine addition to CHO cells also activates S6K1 in a rapamycin-dependent manner (115). mTOR interacts with gephyrin, a tubulin-binding protein involved in neuronal ␥-aminobutyric acid type A (GABA A ) and glycine receptor clustering (117)(118)(119)(120).…”

Section: How Might Tor Signaling Be Involved In Learning and Memory?mentioning

confidence: 99%

The target of rapamycin (TOR) proteins

Raught

Gingras

Sonenberg

2001

Proc. Natl. Acad. Sci. U.S.A.

556

437

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Rapamycin potently inhibits downstream signaling from the target of rapamycin (TOR) proteins. These evolutionarily conserved protein kinases coordinate the balance between protein synthesis and protein degradation in response to nutrient quality and quantity. The TOR proteins regulate (i) the initiation and elongation phases of translation, (ii) ribosome biosynthesis, (iii) amino acid import, (iv) the transcription of numerous enzymes involved in multiple metabolic pathways, and (v) autophagy. Intriguingly, recent studies have also suggested that TOR signaling plays a critical role in brain development, learning, and memory formation. Rapamycin Inhibits Long-Term FacilitationS ynaptic plasticity, the capacity of neurons to modulate the strength of synaptic connections, is believed to be critical for learning and memory formation. Long-term synaptic plasticity (necessary for the formation of long-term memory) requires alterations in gene expression and the establishment of new synaptic connections (1-3). These findings presented an interesting dilemma: That is, how can changes in gene expression in the cell body alter the strength of individual synaptic connections? Recent data suggest that stimulated synapses are ''tagged'' to capture mRNAs produced in the soma and exported throughout the cell (4). Synaptic tagging thus results in localization of mRNAs only to those synapses marked by previous activity. This model also presupposes that long-term plasticity depends on local translation of the localized mRNAs. Indeed, ribosomes, tRNAs, translation initiation factors, and translation elongation factors are found in dendrites (5, 6), and protein synthesis has been demonstrated to occur in isolated synaptic bodies (7,8). Functional studies have demonstrated that protein synthesis is required for potentiation of synaptic transmission elicited by neurotrophic factors in hippocampal slices (9), and for the establishment of long-term facilitation in Aplysia neurons (10). Kandel and coworkers implicated a specific intracellular signaling pathway in this process by demonstrating that serotoninstimulated synaptic protein synthesis can be blocked with rapa-

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“…D 2 R-mediated ERK activation has been reported from different cell types. It is pertussis toxin (PTX)-sensitive and partially blocked by the dominant negative mutant of Ras, N17Ras, in C6 cells (10) and CHO cells (11,12). Phosphatidylinositol (PI) 3-kinase is involved in CHO cells, where the platelet-derived growth factor receptor mediates this through a pathway other than the G␤␥ pathway (11,12).…”

mentioning

confidence: 99%

“…It is pertussis toxin (PTX)-sensitive and partially blocked by the dominant negative mutant of Ras, N17Ras, in C6 cells (10) and CHO cells (11,12). Phosphatidylinositol (PI) 3-kinase is involved in CHO cells, where the platelet-derived growth factor receptor mediates this through a pathway other than the G␤␥ pathway (11,12). Even though molecular details are not yet characterized, it has been reported in CHO cells that the D 3 R-mediated ERK activation, which involves the same signaling pathways as D 2 R, is PTX-sensitive, and PI 3-kinase and atypical PKC are involved (13).…”

mentioning

confidence: 99%

Comparative Studies of Molecular Mechanisms of Dopamine D2 and D3 Receptors for the Activation of Extracellular Signal-regulated Kinase

Beom

Cheong

Torres

et al. 2004

Journal of Biological Chemistry

114

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Extracellular signal-regulated kinase 1 (ERK1) 1 and ERK2 (p44 ERK and p42 ERK ) are key cellular components that control cell proliferation and differentiation (1). The regulation of ERK through G protein-coupled receptors (GPCRs) is a complicated process. Various signaling components play different roles in ERK activation depending on the GPCR and cell types involved (2).There has been substantial progress in the understanding of cellular events that link the activation of GPCR and ERK (for review, see Ref. 1). These signaling events can be classified into several distinct pathways. They include: (i) Ras-dependent activation of ERK via transactivation of receptor-tyrosine kinases (RTKs) such as EGFR, (ii) Ras-independent ERK activation via protein kinase C (PKC) that converges with RTK signaling at the Raf level (iii) activation or inhibition of ERK via the cAMP/ protein kinase A (PKA) pathway, in which the direction of regulation depends on the type of Raf involved, and (iv) the recently substantiated ␤-arrestin-mediated pathway proven in certain classes of GPCRs (3). However, it should be mentioned that these signaling pathways are deduced from the limited sets of individual receptors or cell types, and more extensive and systemic studies are needed for these signaling models to be generalized (4). Among all the dopamine receptor subtypes characterized, it is generally accepted that D 2 R and D 3 R are related to schizophrenia. Possibly because of high similarity in their amino acid composition (46% overall amino acid homology and 78% identity in the transmembrane domains) (5), D 2 R and D 3 R share most signaling pathways such as adenylyl cyclase, extracellular acidification, mitogenesis, ERK activation, inhibition of dopamine synthesis, and ion channel regulation (K ϩ , Ca 2ϩ ) (for review, see Ref. 6). Furthermore, recent studies show that although D 3 R is more densely expressed in the limbic area, mesencephalic dopaminergic neurons express both D 2 R and D 3 R (7-9). Because D 2 R and D 3 R are virtually the same in functional aspect and are expressed in the same cells, it can be speculated that signaling routes or regulatory mechanisms for functions of effectors could be different. To address this issue, we decided to focus on a specific cellular function and conduct a detailed study on signaling mechanisms in order to see if their signaling or regulatory pathways differ. ERK activation was selected as a model experimental system, because GPCRmediated ERK regulation consists of multiple complex steps, which are relatively well established. D 2 R-mediated ERK activation has been reported from different cell types. It is pertussis toxin (PTX)-sensitive and partially blocked by the dominant negative mutant of Ras, N17Ras, in

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Activation of Microtubule‐Associated Protein Kinase (Erk) and p70 S6 Kinase by D₂ Dopamine Receptors

Cited by 74 publications

References 42 publications

Differential regulation of NF‐κB, SRE and CRE by dopamine D1 and D2 receptors in transfected NG108‐15 cells

Differential regulation of NF‐κB, SRE and CRE by dopamine D1 and D2 receptors in transfected NG108‐15 cells

The target of rapamycin (TOR) proteins

Comparative Studies of Molecular Mechanisms of Dopamine D2 and D3 Receptors for the Activation of Extracellular Signal-regulated Kinase

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Activation of Microtubule‐Associated Protein Kinase (Erk) and p70 S6 Kinase by D2 Dopamine Receptors

Cited by 74 publications

References 42 publications

Differential regulation of NF‐κB, SRE and CRE by dopamine D1 and D2 receptors in transfected NG108‐15 cells

Differential regulation of NF‐κB, SRE and CRE by dopamine D1 and D2 receptors in transfected NG108‐15 cells

The target of rapamycin (TOR) proteins

Comparative Studies of Molecular Mechanisms of Dopamine D2 and D3 Receptors for the Activation of Extracellular Signal-regulated Kinase

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Activation of Microtubule‐Associated Protein Kinase (Erk) and p70 S6 Kinase by D₂ Dopamine Receptors