Identification of lung major GTP-binding protein as Gi2 and its distribution in various rat tissues determined by immunoassay

Asano, Taku; Morishita, Rika; Semba, Reiji; Itoh, Hiroshi; Kaziro, Yoshito; Kato, Kanefusa

doi:10.1021/bi00437a035

Cited by 40 publications

(40 citation statements)

References 36 publications

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“…However, G, is located predominantly in the nervous tissues and neuroendocrine cells, while Giz is located in all tissues [30,31]. In the brain, the level of G, was about 15-fold higher than that of Gi2, and the concentrations of Gi2 were constant throughout ontogenic development, while the G, levels markedly increased coincidently with neural development [3 11.…”

Section: Discussionmentioning

confidence: 99%

GABA_B receptors couple to G proteins G_o, G^∗_o and G·_i1 but not to G_i2

1990

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We studied the selectivity of GABAB receptors for coupling to G proteins by testing the ability of various purified G proteins to increase GABA binding to N‐ethylmaleimide (NEM)‐treated membranes of bovine brain. The addition of Go, G∗ o or gi1 to NEM‐treated membranes increased GABA binding in a dose‐dependent manner. However, the addition of Gi2 did not elicit a marked increase in GABA binding. When α subunits of G proteins were mixed with various brain βγ subunit complexes composed of different γ subunits, and they were added to the NEM‐treated membranes, Gi2 with any βγ subunits hardly increased GABA binding. On the other hand, Go with any βγ subunits caused a marked increase, though Go with a small γ subunit was more effective than that with a large γ subunit. These data suggest that the selective coupling of the G proteins to GABAB receptors is determined by the α subunit.

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Section: Discussionmentioning

confidence: 99%

GABA_B receptors couple to G proteins G_o, G^∗_o and G·_i1 but not to G_i2

1990

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“…The amount of G␣ o in cardiac myocytes is 30-to 120-fold lower than in brain (25,26). Unlike the brain, in the rat heart, the G␣ o is not the major G␣ subunit expressed.…”

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confidence: 88%

“…In rat heart, the amount of G␣ s is 0.2 g per mg of protein, while G␣ o is 0.06 g per mg of protein (25). G␣ o is half as abundant as its close relative, G␣ i2 (26). It has not been clear whether it specifically regulated any pathway, nor how redundant is its function with other, more abundant G␣ subunits.…”

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confidence: 99%

Gα _o is necessary for muscarinic regulation of Ca ²⁺ channels in mouse heart

Valenzuela

Han

Mende

et al. 1997

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

136

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Heterotrimeric G proteins, composed of G␣ and G␤␥ subunits, transmit signals from cell surface receptors to cellular effector enzymes and ion channels. The G␣ o protein is the most abundant G␣ subtype in the nervous system, but it is also found in the heart. Its function is not completely known, although it is required for regulation of N-type Ca 2؉ channels in GH 3 cells and also interacts with GAP43, a major protein in growth cones, suggesting a role in neuronal pathfinding. To analyze the function of G␣ o , we have generated mice lacking both isoforms of G␣ o by homologous recombination. Surprisingly, the nervous system is grossly intact, despite the fact that G␣ o makes up 0.2-0.5% of brain particulate protein and 10% of the growth cone membrane. The G␣ o ؊͞؊ mice do suffer tremors and occasional seizures, but there is no obvious histologic abnormality in the nervous system. In contrast, G␣ o ؊͞؊ mice have a clear and specific defect in ion channel regulation in the heart. Normal muscarinic regulation of L-type calcium channels in ventricular myocytes is absent in the mutant mice. The L-type calcium channel responds normally to isoproterenol, but there is no evident muscarinic inhibition. Muscarinic regulation of atrial K ؉ channels is normal, as is the electrocardiogram. The levels of other G␣ subunits (G␣ s , G␣ q , and G␣ i ) are unchanged in the hearts of G␣ o ؊͞؊ mice, but the amount of G␤␥ is decreased. Whichever subunit, G␣ o or G␤␥, carries the signal forward, these studies show that muscarinic inhibition of L-type Ca 2؉ channels requires coupling of the muscarinic receptor to G␣ o . Other cardiac G␣ subunits cannot substitute.Heterotrimeric G proteins, composed of G␣ and G␤␥ subunits, transmit signals from cell surface receptors to cellular effector enzymes and ion channels. One type of G␣ subunit, G␣ o , is extremely abundant in the brain, where it was first identified (1, 2), but it is also expressed in heart, pituitary, and pancreas. In addition to G␣ o , both the brain and the heart contain other closely related G␣ subunits (for example, members of the G␣ i group that are, like G␣ o , substrates for ADP ribosylation by pertussis toxin), as well as G␣ s (which stimulates adenylyl cyclase) and G␣ q (which stimulates phospholipase C␤).The exact function of G␣ o in heart and brain is not known. It is an extremely abundant protein in the nervous system, making up 0.2-0.5% of brain particulate protein (3, 4) and 10% of the growth cone membrane (5). In the nervous system, G␣ o has been postulated to play several roles. The ability of G␣ o to bind GTP␥S can be modulated by GAP43 (neuromodulin), an abundant growth cone protein that is important for neuronal pathfinding (5). Potentially, G␣ o could be part of the signaling cascade that regulates neuronal guidance. Its appearance in the mouse central nervous system is consistent with such a role, since it begins to appear as neurons terminally differentiate and increases as they send out processes (6). The G␣ o protein is conserved in Drosophila, w...

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“…The molecular cloning and sequence analysis of cDNAs have shown that G i has three forms of the α subunit: G i1 α, G i2 α, and G i3 α (Hepler and Gilman 1992). The α subunits of G i1 and G o are widely distributed in the neuropil of the rat brain (Worley et al 1986;Asano et al 1987Asano et al , 1989Terashima et al 1988) and the concentration of G o α in the nervous tissues gradually increases after birth (Asano et al 1988a), while the concentration of G i2 α is constant throughout development (Asano et al 1989). …”

Section: Introductionmentioning

confidence: 99%