Characteristics of Schottky contacts on <i>n</i>-type 4H–SiC using IrO2 and RuO2

Han, Sang Youn; Lee, Jong‐Lam

doi:10.1063/1.1615701

Cited by 29 publications

(19 citation statements)

References 33 publications

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“…Because decreases in basal levels of adenylyl cyclase activity are difficult to detect, we treated the cells concurrently with isoproterenol, which stimulates adenylyl cyclase through endogenous ␤-adrenergic receptors coupled to G␣ s . Consistent with previous studies (18,38), expression of WT RGS16 or WT RGS4 inhibited the negative regulation of adenylyl cyclase activity induced by somatostatin compared with vector-transfected cells (Fig. 2).…”

Section: A Cysteine Residue In the Rgs Box Is Critical For Rgs16supporting

confidence: 79%

Palmitoylation Regulates Regulator of G-protein Signaling (RGS) 16 Function

Osterhout

Waheed

Hiol

et al. 2003

Journal of Biological Chemistry

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Palmitoylation is a reversible post-translational modification used by cells to regulate protein activity. The regulator of G-protein signaling (RGS) proteins RGS4 and RGS16 share conserved cysteine (Cys) residues that undergo palmitoylation. In the accompanying article (Hiol, A., Davey, P. C., Osterhout, J. L., Waheed, A. A., Fischer, E. R., Chen, C. K., Milligan, G., Druey, K. M., and Jones, T. L. Z. (2003) J. Biol. Chem. 278, 19301-19308), we determined that mutation of NH 2 -terminal cysteine residues in RGS16 (Cys-2 and Cys-12) reduced GTPase accelerating (GAP) activity toward a 5-hydroxytryptamine (5-HT 1A )/G␣ o1 receptor fusion protein in cell membranes. NH 2 -terminal acylation also permitted palmitoylation of a cysteine residue in the RGS box of RGS16 (Cys-98). Here we investigated the role of internal palmitoylation in RGS16 localization and GAP activity. Mutation of RGS16 Cys-98 or RGS4 Cys-95 to alanine reduced GAP activity on the 5-HT 1A /G␣ o1 fusion protein and regulation of adenylyl cyclase inhibition. The C98A mutation had no effect on RGS16 localization or GAP activity toward purified G-protein ␣ subunits. Enzymatic palmitoylation of RGS16 resulted in internal palmitoylation on residue Cys-98. Palmitoylated RGS16 or RGS4 WT but not C98A or C95A preincubated with membranes expressing 5-HT 1a /G␣ o1 displayed increased GAP activity over time. These results suggest that palmitoylation of a Cys residue in the RGS box is critical for RGS16 and RGS4 GAP activity and their ability to regulate G i -coupled signaling in mammalian cells.Activation of G-protein-coupled receptors by peptides and hormones catalyzes the exchange of GDP with GTP on the ␣ subunit of its associated heterotrimeric G protein. The active, GTP-bound form of the ␣ subunit interacts with effectors, initiating a signaling cascade. Deactivation of this signaling pathway is mediated by the intrinsic GTPase activity of ␣ subunits, which is in turn accelerated by cognate GTPase activating proteins (GAPs), 1 the regulators of G-protein signaling (RGS proteins) (reviewed in Ref. 1-3).The RGS protein family is large (more than 30 proteins in mammalian cells), and its members share high sequence homology within the conserved RGS domain that confers GAP activity. Regulation of RGS proteins may determine their cellto-cell specificity and preference for certain G-protein ␣ subunits or G-protein-coupled receptor-linked signaling pathways. Modulation of RGS activity may occur by post-translational modifications such as phosphorylation (4 -15) or palmitoylation (16 -23). Indeed, palmitoylation of many G-protein signaling pathway components, from the G-protein-coupled receptors itself to the RGS protein, affects their activity (24 -27).Although the NH 2 and COOH termini were not observed in the crystal structure of RGS4 (28), it is clear that in the case of both RGS4 and RGS16, the amino terminus is also required for function (29 -32). A short amphipathic ␣-helical region in the NH 2 -terminal region of RGS16, conserved in both RGS4 and RGS5, impar...

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Section: A Cysteine Residue In the Rgs Box Is Critical For Rgs16supporting

confidence: 79%

Palmitoylation Regulates Regulator of G-protein Signaling (RGS) 16 Function

Osterhout

Waheed

Hiol

et al. 2003

Journal of Biological Chemistry

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“…However, the mechanism by which RGS proteins recognize GPCRs to confer signaling specificity remains largely unknown. In vitro studies have found that RGS2 shows preference for G q class G ␣ subunits (35), whereas RGS4 attenuates both G i -and G q -mediated signaling (36)(37)(38). Biochemical evidence suggests that the divergent N-terminal domain of RGS proteins participates in GPCR recognition (39), and signaling specificity in vivo is conferred by interaction of RGS proteins with receptor complexes (40).…”

Section: Discussionmentioning

confidence: 99%

Adrenergic modulation of NMDA receptors in prefrontal cortex is differentially regulated by RGS proteins and spinophilin

Liu

Yuen

Allen

et al. 2006

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

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The noradrenergic system in the prefrontal cortex (PFC) is involved in many physiological and psychological processes, including working memory and mood control. To understand the functions of the noradrenergic system, we examined the regulation of NMDA receptors (NMDARs), key players in cognition and emotion, by ␣1-and ␣2-adrenergic receptors (␣1-ARs, ␣2-ARs) in PFC pyramidal neurons. Applying norepinephrine or a norepinephrine transporter inhibitor reduced the amplitude but not paired-pulse ratio of NMDAR-mediated excitatory postsynaptic currents (EPSC) in PFC slices. Specific ␣1-AR or ␣2-AR agonists also decreased NMDAR-EPSC amplitude and whole-cell NMDAR current amplitude in dissociated PFC neurons. The ␣1-AR effect depended on the phospholipase C-inositol 1,4,5-trisphosphate-Ca 2؉ pathway, whereas the ␣2-AR effect depended on protein kinase A and the microtubule-based transport of NMDARs that is regulated by ERK signaling. Furthermore, two members of the RGS family, RGS2 and RGS4, were found to down-regulate the effect of ␣1-AR on NMDAR currents, whereas only RGS4 was involved in inhibiting ␣2-AR regulation of NMDAR currents. The regulating effects of RGS2/4 on ␣1-AR signaling were lost in mutant mice lacking spinophilin, which binds several RGS members and G protein-coupled receptors, whereas the effect of RGS4 on ␣2-AR signaling was not altered in spinophilin-knockout mice. Our work suggests that activation of ␣1-ARs or ␣2-ARs suppresses NMDAR currents in PFC neurons by distinct mechanisms. The effect of ␣1-ARs is modified by RGS2/4 that are recruited to the receptor complex by spinophilin, whereas the effect of ␣2-ARs is modified by RGS4 independent of spinophilin.A drenergic receptors (ARs) can be divided into three main types: ␣1 (␣ 1A-D ), ␣2 (␣ 2A-C ), and ␤ (1-3), based on sequence information, receptor pharmacology, and signaling mechanisms. Although ␤-ARs are located mainly in the cardiovascular system, most ␣1-and ␣2-AR subtypes (except ␣ 1C and ␣ 2B ) are highly expressed in CNS regions, e.g., prefrontal cortex (PFC), hippocampus, and brainstem. Norepinephrine, through the action of ␣1-ARs and ␣2-ARs, has been implicated in many key functions of PFC, including working memory and emotional control (1-3). An aberrant noradrenergic system, complementing altered serotonergic or dopaminergic signaling, contributes significantly to the pathophysiology of a variety of neuropsychiatric diseases associated with PFC dysfunction, such as depression, anxiety, schizophrenia, and attention-deficit hyperactivity disorder (4-7). Therefore, modifying noradrenergic signaling has been considered one of the key therapeutic actions of many antidepressants, anxiolytic drugs, and antipsychotics (8, 9). To understand the functional role of ␣1-and ␣2-ARs, we need to know their cellular targets that are important for cognition and emotion. The NMDAR channel has been implicated in normal cognitive processes and mental disorders (10-12), which makes it a potentially important target by which ␣1-and ␣2-ARs may regulate PFC ...

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“…It was also noticeable that, without PTX treatment, cells expressing the G␣ o RGS/PTXi mutant were more efficiently inhibited by morphine and DAMGO than cells expressing only G␣ o PTXi. In a series of experiments using the opposite approach, expression of RGS4 or G␣-interacting protein in HEK293 cells reduced the level of somatostatin receptor-induced inhibition of cAMP accumulation (31), demonstrating the ability of RGS proteins to control the magnitude of inhibitory G protein signaling. Our data extend this by demonstrating a role for endogenous RGS proteins in this effect.…”

Section: Discussionmentioning

confidence: 99%

Endogenous RGS Protein Action Modulates μ-Opioid Signaling through Gαo

Clark¹,

Harrison²,

Zhong³

et al. 2003

Journal of Biological Chemistry

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RGS (regulators ofGOpioid receptors are a typical seven-transmembrane domain receptor family that signal through inhibitory G proteins to a multitude of second messengers and cellular effectors, including adenylyl cyclase, voltage-operated calcium channels, and inwardly rectifying K ϩ channels (1); intracellular calcium stores (2); and the extracellular signal-regulated kinase (ERK) 1 mitogen-activated protein kinase (MAPK) pathway (3, 4).There are three principal types of opioid receptors, , ␦, and , with ϳ60% homology. However, the -opioid receptor has generated the most interest as the principal site of action for clinical analgesics and abused opiate drugs. The -opioid receptor can couple to all members of the G␣ i/o family, with little selectivity for particular G␣ subunits (5). Selectivity of intracellular -opioid signaling would therefore appear to depend on cell-specific expression of G protein subunits coupled with the selectivity of G proteins to interact with particular effectors. However, it has been suggested that other factors besides G protein and effectors may contribute to signaling specificity (6 -8).Agonist activation of G protein-coupled receptors leads to exchange of GDP for GTP on G␣ and dissociation of the G␣-GTP and G␤␥ subunits. Deactivation is brought about by the intrinsic GTPase activity of G␣, causing GTP to be hydrolyzed to GDP and the subsequent reassociation of the G␣-GDP and G␤␥ subunits. G protein signaling in this fashion is negatively controlled by a family of proteins known as RGS (regulators of G protein signaling) proteins (6). These proteins act as GTPaseactivating proteins (GAPs) for G␣ and speed up the hydrolysis of the G␣-bound GTP, thus reducing the steady-state levels of G␣-GTP and inhibiting signaling. Therefore, it has been suggested that, as with other G protein-coupled receptors, RGS proteins act to inhibit -opioid signaling and may play a controlling role in the effectiveness of opioid receptor ligands. In support of this idea, overexpression of RGS2 shifts the concentration effect curve for morphine-stimulated pigment aggregation to the right to a small (2-fold) degree in cultured dermal melanophores from Xenopus laevis transiently expressing a murine -opioid receptor (9). Furthermore, a reduction in RGS9 levels in mice using antisense oligonucleotide leads to an increase in the anti-nociceptive potency of morphine (10). Although these changes are small, they are suggestive of a role for RGS proteins in opioid coupling efficiency.An important question is whether RGS proteins alter the efficiency of all intracellular signaling pathways equally or whether there is a variable effect that would provide for selectivity. Selectivity for particular pathways may be obtained by several mechanisms. RGS-containing proteins have a wide variety of non-RGS domains (11-13) that, when RGS protein binds to G␣, can link other proteins and signaling pathways to provide for diversity of signaling. In addition, the interaction of RGS protein with receptors may contribute to selectiv...

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Characteristics of Schottky contacts on n-type 4H–SiC using IrO2 and RuO2

Cited by 29 publications

References 33 publications

Palmitoylation Regulates Regulator of G-protein Signaling (RGS) 16 Function

Palmitoylation Regulates Regulator of G-protein Signaling (RGS) 16 Function

Adrenergic modulation of NMDA receptors in prefrontal cortex is differentially regulated by RGS proteins and spinophilin

Endogenous RGS Protein Action Modulates μ-Opioid Signaling through Gαo

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