Melatonin mt1 and MT2 receptors stimulate c-Jun N-terminal kinase via pertussis toxin-sensitive and -insensitive G proteins

Chan, Anthony; Lai, Frank P. L.; Lo, Rico K.H.; Voyno-Yasenetskaya, Tatyana A.; Stanbridge, Eric J.; Wong, Yung Hou

doi:10.1016/s0898-6568(01)00240-6

Cited by 133 publications

(131 citation statements)

References 38 publications

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“…ORL 1 R appears to predominantly utilize a Gbg/Src family kinase-dependent pathway to stimulate JNK, as in the cases for other G i -coupled receptors (Chan et al, 2002). For a synergistic JNK activity to occur, stimulatory signals from the participating systems have to co-operate in a particular manner.…”

Section: Discussionmentioning

confidence: 93%

“…Functional disruption of small GTPases by expression of their dominant-negative mutants (RasS17N, RacT17N, RhoT19N and Cdc42T17N) is an extensively used method to examine their possible involvement (Chan & Wong, 2000;Chan et al, 2002;Kam et al, 2003). Transient expression of RacT17N significantly diminished the JNK activation upon individual and co-stimulation of G i -coupled ORL 1 R and EGFR by OFQ and EGF, respectively ( Figure 5).…”

Section: Asl Chan and Yh Wong Integrated Jnk Activity Modulated Bymentioning

confidence: 99%

“…The reactions were terminated by aspiration of drug-containing medium, followed by the addition of ice-cold 5% trichloroacetic acid (TCA) solution with 1 mM ATP (1 ml per well) and kept at 41C for 1 h. Intracellular levels of [ 3 H]-cAMP were determined by sequential chromatography as described previously (Chan et al, 2002).…”

Section: Assay For Inositol Phosphate (Ip) Formationmentioning

confidence: 99%

“…After that, the cells were stimulated with the appropriated drugs for indicated duration, it was then terminated by washing the cells with phosphate-buffered saline, followed by addition of 500 ml of ice-cold detergent-containing lysis buffer (50 mM Tris-HCl, pH 7.5, 100 mM NaCl, 5 mM EDTA, 40 mM NaP 2 O 7 , 1% Triton X-100, 1 mM DTT, 200 mM Na 3 VO 4 , 100 mM PMSF, 2 mg ml À1 leupeptin, 4 mg ml À1 aprotinin and 0.7 mg ml À1 pepstatin). Lysates obtained were subjected to JNK assay as described previously (Chan et al, 2002;Kam et al, 2003).…”

Section: In Vitro Jnk Assaymentioning

confidence: 99%

“…This can be demonstrated by their stimulatory or inhibitory effects on adenylyl cyclase and PLC. In total, 12 GPCRs were examined in Cos-7 cells ( Receptors specifically coupled to G i , but not G s and G q , induced synergistic JNK activation upon co-stimulation of EGFR by EGF Recent studies demonstrated that both GPCRs and RTKs are linked to activation of JNK (Logan et al, 1997;Chan et al, 2002); in order to examine how these two transmembrane signaling systems co-operate in the regulation of this kinase activity, we transfected Cos-7 cells which endogenously express EGFR, with HA-tagged JNK and GPCRs of different coupling specificities. EGF treatment was associated with a roughly doubled JNK activity, while stimulation of GPCRs induced kinase activation of different magnitudes, with B2-fold induction for G i , B1.5-fold for G s and B6-fold for G q -coupled receptors as compared to their basal responses which were defined as 1.0-fold of the kinase activity (Table 1).…”

Section: Regulation Of Phospholipase C and Adenylyl Cyclase Activitiementioning

confidence: 99%

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Epidermal growth factor differentially augments G_i‐mediated stimulation of c‐Jun N‐terminal kinase activity

Chan

Wong

2004

British J Pharmacology

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1 Signaling networks involving different receptor systems allow extracellular signals to be integrated and transformed into various biological activities. In this report, we studied the activity of the c-Jun N-terminal kinase (JNK) subgroup of mitogen-activated protein kinases (MAPKs), in response to stimulation by G protein-coupled receptors (GPCRs) and co-activation with epithermal growth factor receptor (EGFR). 2 Stimulation of exogenous GPCRs in Cos-7 cells induced JNK activation of different magnitudes depending on their G-protein coupling specificities (G q 4G i 4G s ), and a moderate JNK activation was linked to stimulation of endogenous EGFR by EGF. 3 Co-stimulation with GPCR agonists and EGF resulted in differential augmentation of JNK activities, with G i -coupled receptors associated with a synergistic JNK activation upon co-stimulation with EGF, while G q -and G s -coupled receptors were incapable of triggering this effect. 4 This G i /EGF-induced synergistic JNK activation was inhibited by pertussis toxin and AG1478, and may involve Src family tyrosine kinases, PI3 K, Ca 2 þ /calmodulin and small GTPases as important intermediates, while Ca 2 þ mobilization was triggered by the stimulation of G q -coupled receptor or EGF treatment, but not by the G i -or G s -coupled receptors. 5 Transient expression of Gbg subunits with EGF treatment, or co-activation of exogenous G icoupled receptor with thapsigargin also resulted in a synergistic JNK activation. Activation of G icoupled receptor accompanied with EGF treatment enhanced the expression level and activity of MAPK phosphatase type I, which occurred after the maximal synergistic JNK activation. 6 Our results support a mechanistic model where EGF signaling may differentially regulate the JNK activities triggered by GPCRs of different coupling specificities.

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Section: Discussionmentioning

confidence: 93%

Section: Asl Chan and Yh Wong Integrated Jnk Activity Modulated Bymentioning

confidence: 99%

Section: Assay For Inositol Phosphate (Ip) Formationmentioning

confidence: 99%

Section: In Vitro Jnk Assaymentioning

confidence: 99%

Section: Regulation Of Phospholipase C and Adenylyl Cyclase Activitiementioning

confidence: 99%

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Epidermal growth factor differentially augments G_i‐mediated stimulation of c‐Jun N‐terminal kinase activity

Chan

Wong

2004

British J Pharmacology

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Melatonin Receptors in Central Nervous System

Dubocovich

2007

Handbook of Contemporary Neuropharmacology

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The functional role of melatonin receptors in the mammalian central nervous system and their therapeutic potential is discussed. Melatonin, dubbed the “hormone of darkness,” is produced primarily in the pineal gland and retina following circadian rhythms with high levels of night. The chapter describes the structure, molecular pharmacology, signaling, and function of the MT1 and MT2 mammalian melatonin receptors. This is followed by discussion of recent advances in the regulation of melatonin receptor sensitivity and its role in circadian rhythm modulation by the circadian timing system. Recent advances in the discovery and development of therapeutic agents targeting melatonin receptors for the treatment of insomnia, circadian rhythm dysfunctions, and depression are also highlighted.

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Melatonin: Signaling mechanisms of a pleiotropic agent

2009

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Melatonin acts both as a hormone of the pineal gland and as a local regulator molecule in various tissues. Quantities of total tissue melatonin exceed those released from the pineal. With regard to this dual role, to the orchestrating, systemic action on various target tissues, melatonin is highly pleiotropic. Numerous secondary effects result from the control of the circadian pacemaker and, in seasonal breeders, of the hypothalamic/pituitary hormonal axes. In mammals, various binding sites for melatonin have been identified, the membrane receptors MT(1) and MT(2), which are of utmost chronobiological importance, ROR and RZR isoforms as nuclear receptors from the retinoic acid receptor superfamily, quinone reductase 2, calmodulin, calreticulin, and mitochondrial binding sites. The G protein-coupled receptors (GPCRs) MT(1) and MT(2) are capable of parallel or alternate signaling via different Galpha subforms, in particular, Galpha(i) (2/) (3) and Galpha(q), and via Gbetagamma, as well. Multiple signaling can lead to the activation of different cascades and/or ion channels. Melatonin frequently decreases cAMP, but also activates phospholipase C and protein kinase C, acts via the MAP kinase and PI3 kinase/Akt pathways, modulates large conductance Ca(2+)-activated K(+) and voltage-gated Ca(2+) channels. MT(1) and MT(2) can form homo and heterodimers, and MT(1) interacts with other proteins in the plasma membrane, such as an orphan GPCR, GPR50, and the PDZ domain scaffolding protein MUPP1, effects which negatively or positively influence signaling capacity. Cross-talks between different signaling pathways, including influences of the membrane receptors on nuclear binding sites, are discussed. (c) 2009 International Union of Biochemistry and Molecular Biology, Inc.

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Melatonin mt1 and MT2 receptors stimulate c-Jun N-terminal kinase via pertussis toxin-sensitive and -insensitive G proteins

Cited by 133 publications

References 38 publications

Epidermal growth factor differentially augments G_i‐mediated stimulation of c‐Jun N‐terminal kinase activity

Epidermal growth factor differentially augments G_i‐mediated stimulation of c‐Jun N‐terminal kinase activity

Melatonin Receptors in Central Nervous System

Melatonin: Signaling mechanisms of a pleiotropic agent

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Melatonin mt1 and MT2 receptors stimulate c-Jun N-terminal kinase via pertussis toxin-sensitive and -insensitive G proteins

Cited by 133 publications

References 38 publications

Epidermal growth factor differentially augments Gi‐mediated stimulation of c‐Jun N‐terminal kinase activity

Epidermal growth factor differentially augments Gi‐mediated stimulation of c‐Jun N‐terminal kinase activity

Melatonin Receptors in Central Nervous System

Melatonin: Signaling mechanisms of a pleiotropic agent

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Epidermal growth factor differentially augments G_i‐mediated stimulation of c‐Jun N‐terminal kinase activity

Epidermal growth factor differentially augments G_i‐mediated stimulation of c‐Jun N‐terminal kinase activity