G Alpha-q/11 Protein Plays a Key Role in Insulin-Induced Glucose Transport in 3T3-L1 Adipocytes

Imamura, Teruhiko; Vollenweider, Péter; Egawa, Katsuya; Clodi, Martin; Ishibashi, Keiichiro; Nakashima, Naoki; Ugi, Satoshi; Adams, John W.; Brown, Joan Heller; Olefsky, Jerrold M.

doi:10.1128/mcb.19.10.6765

Cited by 160 publications

(185 citation statements)

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“…The addition of IGF-1 increased G␣ and decreases G␤␥ association to IGF-1R. The IGF-1R appears to utilize a G␣ from the Gi subfamily, whereas the insulin receptor appears to utilize a Gq/11 subfamily member because insulin addition stimulated Gq phosphorylation (Imamura et al, 1999). Moreover, the expression of a constitutively active Gq conferred a constitutively active IGF-1 response and injected anti-Gq antibody blocked the insulin response.…”

Section: Discussionmentioning

confidence: 93%

Role of a Heterotrimeric G Protein in Regulation of Arabidopsis Seed Germination

et al. 2002

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Seed germination is regulated by many signals. We investigated the possible involvement of a heterotrimeric G protein complex in this signal regulation. Seeds that carry a protein null mutation in the gene encoding the alpha subunit of the G protein in Arabidopsis (GPA1) are 100-fold less responsive to gibberellic acid (GA), have increased sensitivity to high levels of Glc, and have a near-wild-type germination response to abscisic acid and ethylene, indicating that GPA1 does not directly couple these signals in germination control. Seeds ectopically expressing GPA1 are at least a million-fold more responsive to GA, yet still require GA for germination. We conclude that the GPA1 indirectly operates on the GA pathway to control germination by potentiation. We propose that this potentiation is directly mediated by brassinosteroids (BR) because the BR response and synthesis mutants, bri1-5 and det2-1, respectively, share the same GA sensitivity as gpa1 seeds. Furthermore, gpa1 seeds are completely insensitive to brassinolide rescue of germination when the level of GA in seeds is reduced. A lack of BR responsiveness is also apparent in gpa1 roots and hypocotyls suggesting that BR signal transduction is likely coupled by a heterotrimeric G protein at various points in plant development.Seeds integrate many intrinsic signals to control germination (Koornneef et al., 2002). For example, since the original observation by Chrispeels and Varner (1966), it has been repeatedly shown that GA induces germination and that abscisic acid (ABA) antagonizes the GA effect (Koornneef and Van der Veen, 1980;Karssen et al., 1989; Gilroy and Jones, 1994;Ritchie and Gilroy, 1998;Lovegrove and Hooley, 2000). Seed germination of GA synthesis mutants can be rescued by the application of GA and ABA synthesis and insensitive mutants lack the ABA inhibition of GA-induced germination as well as being viviparous (Koornneef et al., 1982(Koornneef et al., , 1984 Finkelstein and Somerville, 1990;Koornneef and Karssen, 1994;Leon-Kloosterziel et al., 1996). Brassinosteroid (BR) probably acts downstream of GA because BR is able to rescue germination of GA-deficient (Steber and McCourt, 2001) and GA response (Steber et al., 1998) mutant seeds. These authors argue that the BR input is likely to reside upstream of ABA's attenuating effect on GA-induced germination because BR synthesis and response mutants have slightly altered ABA sensitivity.The inhibitory effect of high concentrations of sugars on germination may occur via ABA. The evidence supporting this comes from measurements of ABA in Glc-treated seedlings (Arenas-Huertero et al., 2000) and from the observation that ABA synthesis and response mutants are insensitive to Glc (Laby et al., 2000;Rook et al., 2001). Ethylene controls the Glc inhibition of germination (Zhou et al., 1998). Evidence supporting this includes the observations that high concentrations of ethylene antagonize the Glc repression of germination (Ghassemian et al., 2000), the ctr1 (constitutive ethylene response mutant; Gibs...

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Section: Discussionmentioning

confidence: 93%

Role of a Heterotrimeric G Protein in Regulation of Arabidopsis Seed Germination

et al. 2002

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“…Phosphorylation of Gaq/11 by the insulin receptor activates PI3K, thus, stimulating GLUT4-mediated glucose uptake. This signaling pathway is inhibited by G-protein-coupled receptor kinase-2 (Grk2) which binds and inhibits the Ga subunit of Gaq/11 [11,12]. Finally, the proto-oncogene product, Cbl, is recruited to the insulin receptor by the adapter protein Cbl associated protein (CAP) and the CAP/Cbl complex can mediate cell surface translocation of GLUT4 independent of PI3K activity [13].…”

Section: Non-irs-mediated Insulin Signalingmentioning

confidence: 99%

Inflammation and insulin resistance

2007

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Obesity-induced chronic inflammation is a key component in the pathogenesis of insulin resistance and the Metabolic syndrome. In this review, we focus on the interconnection between obesity, inflammation and insulin resistance. Proinflammatory cytokines can cause insulin resistance in adipose tissue, skeletal muscle and liver by inhibiting insulin signal transduction. The sources of cytokines in insulin resistant states are the insulin target tissue themselves, primarily fat and liver, but to a larger extent the activated tissue resident macrophages. While the initiating factors of this inflammatory response remain to be fully determined, chronic inflammation in these tissues could cause localized insulin resistance via autocrine/paracrine cytokine signaling and systemic insulin resistance via endocrine cytokine signaling all of which contribute to the abnormal metabolic state.

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“…In this respect, G q/11 has been shown to transmit signals to activate PI3K. 51,52 Furthermore, inhibition of PI3K with LY294002 reduces LPC/G2A-mediated chemotaxis (L.V.Y. and O.N.W., unpublished observations, October 2003).…”

Section: G I -Independent Pathways In Cell Migrationmentioning

confidence: 99%

Gi-independent macrophage chemotaxis to lysophosphatidylcholine via the immunoregulatory GPCR G2A

Yang

Radu

Wang

et al. 2005

Blood

161

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G2A is a G-protein–coupled receptor (GPCR) involved in immune regulation. Previous studies have shown that lysophosphatidylcholine (LPC), a bioactive lipid associated with atherosclerosis and autoimmunity, acts through G2A to induce diverse biologic effects. Production of LPC during cell apoptosis serves as a chemotactic signal for macrophage recruitment. Here we demonstrate that macrophage chemotaxis to LPC is dependent on G2A function. Wild-type but not G2A-deficient mouse peritoneal macrophages migrated toward LPC. RNAi-mediated knockdown of G2A in J774A.1 macrophages abolished LPC-induced chemotaxis, whereas overexpression of G2A significantly enhanced this process. Mutation of the conserved DRY motif of G2A resulted in loss of chemotaxis to LPC, suggesting a requirement for G-protein signaling. Unlike most GPCRs, including the chemokine receptors, coupling to Gi is not required for LPC/G2A-mediated chemotaxis, but coupling to Gq/11 and G12/13 is necessary as judged by inhibition with dominant negative forms of these alpha subunits or with regulators of G-protein signaling (RGS) constructs. Collectively, these data establish that pertussis toxin–insensitive G2A signaling regulates macrophage chemotaxis to LPC. Defects in this signaling pathway may be related to the pathogenesis of systemic autoimmune disease.

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G Alpha-q/11 Protein Plays a Key Role in Insulin-Induced Glucose Transport in 3T3-L1 Adipocytes

Cited by 160 publications

References 27 publications

Role of a Heterotrimeric G Protein in Regulation of Arabidopsis Seed Germination

Role of a Heterotrimeric G Protein in Regulation of Arabidopsis Seed Germination

Inflammation and insulin resistance

Gi-independent macrophage chemotaxis to lysophosphatidylcholine via the immunoregulatory GPCR G2A

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