• Title/Summary/Keyword: $G_{\alpha}q$

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Direct Involvement of G Protein $\alpha_{q/11}$ Subunit in Regulation of Muscarinic Receptor-Mediated sAPP$\alpha$ Release

  • Kim Jin Hyoung;Kim Hwa-Jung
    • Archives of Pharmacal Research
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    • v.28 no.11
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    • pp.1275-1281
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    • 2005
  • The $G_{q/11}$ protein-coupled receptors, such as muscarinic (M1 & M3) receptors, have been shown to regulate the release of a soluble amyloid precursor protein (sAPP$\alpha$) produced from $\alpha$-secretase processing. However, there is no direct evidence for the precise characteristics of G proteins, and the signaling mechanism for the regulation of $G_{q/11}$ protein-coupled receptor mediated sAPP$\alpha$ release is not clearly understood. This study examined whether the muscarinic receptor-mediated release of sAPP$\alpha$ is directly regulated by $G\alpha_{q/11}$ proteins. The HEK293 cells were transiently cotransfected with muscarinic M3 receptors and a dominant-negative minigene construct of the G protein $\alpha$ subunit. The sAPP$\alpha$ release in the media was measured using an antibody specific for sAPP. The sAPP$\alpha$ release enhancement induced by muscarinic receptor stimulation was decreased by a $G_{q/11}$ minigene construct, whereas it was not blocked by a control minigene construct (the G$\alpha$ carboxy peptide in random order, G$\alpha_{q}$R) or $G\alpha_{j}$ constructs. This indicated a direct role of the $G\alpha_{q/11}$ protein in the regulation of muscarinic M3 receptor-mediated sAPP$\alpha$ release. We also investigated whether the transactivation of the epidermal growth factor receptor (EGFR) by a muscarinic agonist could regulate the sAPP$\alpha$ release in SH-SY5Y cells. Pretreatment of a specific EGFR kinase inhibitor, tyrophostin AG1478 (250 nM), blocked the EGF-stimulated sAPP$\alpha$ release, but did not block the oxoM­stimulated sAPP$\alpha$ release. This demonstrated that the transactivation of the EGFR by muscarinic receptor activation was not involved in the muscarinic receptor-mediated sAPP$\alpha$ release.

ON HYPERHOLOMORPHIC Fαω,G(p, q, s) SPACES OF QUATERNION VALUED FUNCTIONS

  • Kamal, Alaa;Yassen, Taha Ibrahim
    • Korean Journal of Mathematics
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    • v.26 no.1
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    • pp.87-101
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    • 2018
  • The purpose of this paper is to define a new class of hyperholomorphic functions spaces, which will be called $F^{\alpha}_{{\omega},G}$(p, q, s) type spaces. For this class, we characterize hyperholomorphic weighted ${\alpha}$-Bloch functions by functions belonging to $F^{\alpha}_{{\omega},G}$(p, q, s) spaces under some mild conditions. Moreover, we give some essential properties for the extended weighted little ${\alpha}$-Bloch spaces. Also, we give the characterization for the hyperholomorphic weighted Bloch space by the integral norms of $F^{\alpha}_{{\omega},G}$(p, q, s) spaces of hyperholomorphic functions. Finally, we will give the relation between the hyperholomorphic ${\mathcal{B}}^{\alpha}_{{\omega},0}$ type spaces and the hyperholomorphic valued-functions space $F^{\alpha}_{{\omega},G}$(p, q, s).

Possible target for G protein antagonist: Identification of specific amino acid residue responsible for the molecular interaction of G$\alpha$ 16 with chemoattractant C5a receptor.

  • 이창호
    • Proceedings of the Korean Society of Applied Pharmacology
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    • 2000.04a
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    • pp.17-19
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    • 2000
  • Heterotrimeric G Proteins transduce ligand binding to a wide variety of seven transmembrane cell surface receptors into intracellular signals. The currently accepted model for the activation of G protein suggests that ligand-activated receptor accelerates GDP-GTP exchange reactions on the ${\alpha}$ subunit of the heterotrimeric G protein. At least seventeen distinct isoforms of the G${\alpha}$ subunit protein have been identified in mammalian organisms. Among them, the G${\alpha}$q family consists of five members whose ${\alpha}$ subunits show different expression patterns. G${\alpha}$q and G${\alpha}$11 seem to be almost ubiquitously expressed, whereas G${\alpha}$14 is predominantly expressed in spleen, lung, kidney and testis. G${\alpha}$16 and its murine counterpart G${\alpha}$15 are expressed in hematopoietic cells and has been shown to couple a wide variety of receptors to phosphoinositide-specific phospholipase C activity. Beta-isoforms of phospholipase C were shown to be activated by all members of G${\alpha}$q family, i.e., G${\alpha}$q, G${\alpha}$11, G${\alpha}$l4 and G${\alpha}$16 subunits either in reconstitution system. or in experiments using cDNA transfection with intact Cos-7 cells.

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Differential Coupling of G$\alpha$q Family of G-protein to Muscarinic $M_1$ Receptor and Neurokinin-2-Receptor

  • Lee, Chang-Ho;Shin, In-Chul;Kang, Ju-Seop;Koh, Hyun-Chul;Ha, Ji-Hee;Min, Chul-Ki
    • Archives of Pharmacal Research
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    • v.21 no.4
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    • pp.423-428
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    • 1998
  • The ligand binding signals to a wide variety of seven transmembrane cell surface receptors are transduced into intracellular signals through heterotrimeric G-proteins. Recently, there have been reports which show diverse coupling patterns of ligand-activated receptors to the members of Gq family $\alpha$ subunits. In order to shed some light on these complex signal processing networks, interactions between G$\alpha$q family of G protein and neurokinin-2 receptor as well as muscarinic M$_{1}$ receptor, which are considered to be new thearpeutic targets in asthma, were studied. Using washed membranes from Cos-7 cells co-transfected with different G.alpha.q and receptor cDNAs, the receptors were stimulated with various concentrations of carbachol and neurokinin A and the agonist-dependent release of [$^3H$]inositol phosphates through phospholipase C beta-1 activation was measured. Differential coupling of Gaq family of G-protein to muscarinic M$_{1}$ receptor and neurokinin-2 receptor was observed. The neurokinin-2 receptor shows a ligand-mediated response in membranes co-transfected with G$\alpha$q, G$\alpha$11 and G$\alpha$14 but not G$\alpha$16 and the ability of the muscarinic $M_1$ receptor to activate phospholipase C through G$\alpha$/11 but not G$\alpha$14 and G$\alpha$16 was demonstrated. Clearly G$\alpha$/11 can couple $\M_1$ and neurokinin-2 receptor to activate phospholipase C. But, there are differences in the relative coupling of the G$\alpha$14 and G$\alpha$16 subunits to these receptors.

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3-DESIGNS DERIVED FROM PLANE ALGEBRAIC CURVES

  • Yu, Ho-Seog
    • Bulletin of the Korean Mathematical Society
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    • v.44 no.4
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    • pp.817-823
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    • 2007
  • In this paper, we develop a simple method for computing the stabilizer subgroup of a subgroup of $$D(g)={{\alpha}{\in}\mathbb{F}_q|there\;is\;a\;{\beta}{\in}{\mathbb{F}}^x_q\;such\;that\;{\beta}^n=g(\alpha)}$$ in $PSL_2(\mathbb{F}_q)$, where q is a large odd prime power, n is a positive integer dividing q-1, and $g(x){\in}\mathbb{F}_q[x]$. As an application, we construct new infinite families of 3-designs (cf. Examples 3.4 and 3.5).

A Class of Bilateral Generating Functions for the Jacobi Polynomial

  • SRIVASTAVA, H M.
    • Journal of the Korean Mathematical Society
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    • v.8 no.1
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    • pp.25-30
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    • 1971
  • Put ($$^*$$) $$G[x,y]={\sum}\limits^{p+q=n}_{p,q=0}[-n]_{p+q}c_{p,q}x^py^q$$, where $[{\lambda}]_m$ is the Pocbhammer symbol and the $c_{p,q}$ are arbitrary constants. Making use of the specialized forms of some of his earlier results (see [8] and [9] the author derives here bilateral generating functions of the type ($$^{**}$$) $${\sum}\limits^{\infty}_{n=0}{\frac{[\lambda]_n}{n!}}_2F_1[\array{{\rho}-n,\;{\alpha};\\{\lambda}+{\rho};}x]\;G[y,z]t^n$$ where ${\alpha}$, ${\rho}$ and ${\lambda}$ are arbitrary complex numbers. In particular, it is shown that when G[y, z] is a double hypergeometric polynomial, the right-band member of ($^{**}$) belongs to a class of general triple hypergeometric functions introduced by the author [7]. An interesting special case of ($^{**}$) when ${\rho}=-m,\;m$ being a nonnegative integer, yields a class of bilateral generating functions for the Jacobi polynomials $\{P_n{^{{\alpha},{\beta}}}(x)\}$ in the form ($$^{***}$$) $${\sum\limits^{\infty}_{n=0}}\(\array{m+n\\n}\)P{^{({\alpha}-n,{\beta}-n)}_{m+n}(x)\;G[y,z]{\frac{t^n}{n!}}$$, which provides a unification of several known results. Further extensions of ($^{**}$) and ($^{***}$) with G[y, z] replaced by an analogous multiple sum $H\[y_1,{\cdots},y_m\]$ are also discussed.

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The Signal Transduciton of Ginsenosides, Active Ingredients of Panax ginseng, in Xenopus oocyte: A Model System for Ginseng Study

  • Nah Seung-Yeol;Lee Sang-Mok
    • Proceedings of the Ginseng society Conference
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    • 2002.10a
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    • pp.66-83
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    • 2002
  • Recently, we have provided evidence that ginsenosides, the active components of Panax ginseng, utilize pertussis toxin (PTX)-insensitive $G{\alpha}_{q/11}-phospholipase\;C-{\beta}3(PLC-{\beta}3)$ signal transduction pathway for the enhancement of $Ca^{2+}-activated\;Cl^{-}$ current in the Xenopus oocyte (British J. Pharmacol. 132, 641-647, 2001; JBC 276, 48797-48802, 2001). Other investigators have shown that stimulation of receptors linked to $G{\alpha}-PLC$ pathway inhibits the activity of G proteincoupled inwardly rectifying $K^+$ (GIRK) channel. In the present study, we sought to determine whether ginsenosides influenced the activity of GIRK 1 and GIRK 4 (GIRK 1/4) channels expressed in the Xenopus oocyte, and if so, the underlying signal transduction mechanism. In oocyte injected with GIRK 1/4 channel cRNAs, bath-applied ginsenosides inhibited high potassium (HK) solution-elicited GIRK current $(EC_{50}:4.9{\pm}4.3\;{\mu}g/ml).$ Pretreatment of the oocyte with PTX reduced the HK solution-elicited GIRK current by $49\%,$ but it did not alter the inhibitory ginsenoside effect on GIRK current. Prior intraoocyte injection of cRNA(s) coding $G{\alpha}_q,\;G{\alpha}_{11}\;or\;G{\alpha}_q/G{\alpha}_{11},\;but\;not\;G{\alpha}_{i2}\;or\;G{\alpha}_{oA}$ attenuated the inhibitory ginsenoside effect. Injection of cRNAs coding $G{\beta}_{1{\gamma}2}$ also attenuated the ginsenoside effect. Similarly, injection of the cRNAs coding regulators of G protein signaling 1, 2 and 4 (RGS1, RGS2 and RGS4), which interact with $G{\alpha}_i\;and/or\;G{\alpha}_{q/11}$ and stimulates the hydrolysis of GTP to GDP in active GTP-bound $G{\alpha}$ subunit, resulted in a significant reduction of ginsenoside effect on GIRK current. Preincubation of GIRK channel-expressing oocyte in PLC inhibitor (U73122) or protein kinase C (PKC) inhibitor (staurosporine or chelerythrine) blocked the inhibitory ginsenoside effect on GIRK current. On the other hand, intraoocyte injection of BAPTA, a free $Ca^{2+}$ chelator, had no significant effect on the ginsenoside action. Taken together, these results suggest that ginsenosides inhibit the activity of GIRK 1/4 channel expressed in the Xenopus oocyte through a PTX-insensitive and $G{\alpha}_{q/11}$-,PLC-and PKC-mediated signal transduction pathway.

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ON THE EXISTENCE OF POSITIVE SOLUTION FOR A CLASS OF NONLINEAR ELLIPTIC SYSTEM WITH MULTIPLE PARAMETERS AND SINGULAR WEIGHTS

  • Rasouli, S.H.
    • Communications of the Korean Mathematical Society
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    • v.27 no.3
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    • pp.557-564
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    • 2012
  • This study concerns the existence of positive solution for the following nonlinear system $$\{-div(|x|^{-ap}|{\nabla}u|^{p-2}{\nabla}u)=|x|^{-(a+1)p+c_1}({\alpha}_1f(v)+{\beta}_1h(u)),x{\in}{\Omega},\\-div(|x|^{-bq}|{\nabla}v|q^{-2}{\nabla}v)=|x|^{-(b+1)q+c_2}({\alpha}_2g(u)+{\beta}_2k(v)),x{\in}{\Omega},\\u=v=0,x{\in}{\partial}{\Omega}$$, where ${\Omega}$ is a bounded smooth domain of $\mathbb{R}^N$ with $0{\in}{\Omega}$, 1 < $p,q$ < N, $0{{\leq}}a<\frac{N-p}{p}$, $0{{\leq}}b<\frac{N-q}{q}$ and $c_1$, $c_2$, ${\alpha}_1$, ${\alpha}_2$, ${\beta}_1$, ${\beta}_2$ are positive parameters. Here $f,g,h,k$ : $[0,{\infty}){\rightarrow}[0,{\infty})$ are nondecresing continuous functions and $$\lim_{s{\rightarrow}{\infty}}\frac{f(Ag(s)^{\frac{1}{q-1}})}{s^{p-1}}=0$$ for every A > 0. We discuss the existence of positive solution when $f,g,h$ and $k$ satisfy certain additional conditions. We use the method of sub-super solutions to establish our results.

q-SOBOLEV ORTHOGONALITY OF THE q-LAGUERRE POLYNOMIALS {Ln(-N)(·q)}n=0 FOR POSITIVE INTEGERS N

  • Moreno, Samuel G.;Garcia-Caballe, Esther M.
    • Journal of the Korean Mathematical Society
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    • v.48 no.5
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    • pp.913-926
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    • 2011
  • The family of q-Laguerre polynomials $\{L_n^{(\alpha)}({\cdot};q)\}_{n=0}^{\infty}$ is usually defined for 0 < q < 1 and ${\alpha}$ > -1. We extend this family to a new one in which arbitrary complex values of the parameter ${\alpha}$ are allowed. These so-called generalized q-Laguerre polynomials fulfil the same three term recurrence relation as the original ones, but when the parameter ${\alpha}$ is a negative integer, no orthogonality property can be deduced from Favard's theorem. In this work we introduce non-standard inner products involving q-derivatives with respect to which the generalized q-Laguerre polynomials $\{L_n^{(-N)}({\cdot};q)\}_{n=0}^{\infty}$, for positive integers N, become orthogonal.