scholarly journals Paternal versus maternal transmission of a stimulatory G-protein α subunit knockout produces opposite effects on energy metabolism

2000 ◽  
Vol 105 (5) ◽  
pp. 615-623 ◽  
Author(s):  
Shuhua Yu ◽  
Oksana Gavrilova ◽  
Hui Chen ◽  
Randy Lee ◽  
Jie Liu ◽  
...  
Keyword(s):  
Energy Metabolism ◽  
G Protein ◽  
Maternal Transmission ◽  
Α Subunit ◽  
Stimulatory G Protein ◽  
G Protein Α Subunit

scholarly journals Receptor-Mediated Adenylyl Cyclase Activation Through XLαs, the Extra-Large Variant of the Stimulatory G Protein α-Subunit

2002 ◽  
Vol 16 (8) ◽  
pp. 1912-1919 ◽  
Author(s):  
Murat Bastepe ◽  
Yasemin Gunes ◽  
Beatriz Perez-Villamil ◽  
Joy Hunzelman ◽  
Lee S. Weinstein ◽  
...  
Keyword(s):  
Adenylyl Cyclase ◽  
G Protein ◽  
Adrenergic Receptor ◽  
Α Subunit ◽  
Exon 2 ◽  
Amino Terminal ◽  
Stimulatory G Protein ◽  
Β2 Adrenergic Receptor ◽  
Carboxyl Terminal ◽  
G Protein Α Subunit

Abstract XLαs, the large variant of the stimulatory G protein α subunit (Gsα), is derived from GNAS1 through the use of an alternative first exon and promoter. Gsα and XLαs have distinct amino-terminal domains, but are identical over the carboxyl-terminal portion encoded by exons 2–13. XLαs can mimic some functions of Gsα, including βγ interaction and adenylyl cyclase stimulation. However, previous attempts to demonstrate coupling of XLαs to typically Gs-coupled receptors have not been successful. We now report the generation of murine cell lines that carry homozygous disruption of Gnas exon 2, and are therefore null for endogenous XLαs and Gsα (GnasE2−/E2−). GnasE2−/E2− cells transfected with plasmids encoding XLαs and different heptahelical receptors, including the β2-adrenergic receptor and receptors for PTH, TSH, and CRF, showed agonist-mediated cAMP accumulation that was indistinguishable from that observed with cells transiently coexpressing Gsα and these receptors. Our findings thus indicate that XLαs is capable of functionally coupling to receptors that normally act via Gsα.

scholarly journals The Stimulatory G Protein α-Subunit Gsα Is Imprinted in Human Thyroid Glands: Implications for Thyroid Function in Pseudohypoparathyroidism Types 1A and 1B

2003 ◽  
Vol 88 (9) ◽  
pp. 4336-4341 ◽  
Author(s):  
Jie Liu ◽  
Beth Erlichman ◽  
Lee S. Weinstein
Keyword(s):  
G Protein ◽  
Human Thyroid ◽  
Pcr Analysis ◽  
Specific Expression ◽  
Α Subunit ◽  
Albright Hereditary Osteodystrophy ◽  
Camp Generation ◽  
Gsα Gene ◽  
Stimulatory G Protein ◽  
G Protein Α Subunit

The stimulatory G protein α-subunit Gsα couples receptors to adenylyl cyclase and is required for hormone-stimulated cAMP generation. In Albright hereditary osteodystrophy, heterozygous Gsα null mutations only lead to PTH, TSH, and gonadotropin resistance when inherited maternally [pseudohypoparathyroidism type 1A; (PHP1A)]. Maternal-specific expression of Gsα in specific hormone targets could explain this observation. Using hot-stop PCR analysis on total RNA from six normal human thyroid specimens, we showed that the majority of the Gsα mRNA (72 ± 3%) was derived from the maternal allele. This is consistent with the presence of TSH resistance in patients with maternal Gsα null mutations (PHP1A) and the absence of TSH resistance in patients with paternal Gsα mutations (pseudopseudohypoparathyroidism). Patients with PTH resistance in the absence of Albright hereditary osteodystrophy (PHP1B) have an imprinting defect of the Gsα gene resulting in both alleles having a paternal epigenotype, which would lead to a more moderate level of thyroid-specific Gsα deficiency. We found evidence of borderline TSH resistance in 10 of 22 PHP1B patients. This study provides further evidence for tissue-specific imprinting of Gsα in humans and provides a potential mechanism for mild to moderate TSH resistance in PHP1A and borderline resistance in some patients with PHP1B.

Stimulatory G-protein α-subunit mRNA levels are not increased in autopsied cerebral cortex from patients with bipolar disorder

1996 ◽  
Vol 42 (1) ◽  
pp. 45-50 ◽  
Author(s):  
L. Trevor Young ◽  
Vida Asghari ◽  
Peter P. Li ◽  
Stephen J. Kish ◽  
Margaret Fahnestock ◽  
...  
Keyword(s):  
Bipolar Disorder ◽  
Cerebral Cortex ◽  
G Protein ◽  
Mrna Levels ◽  
Α Subunit ◽  
Subunit Mrna ◽  
Stimulatory G Protein ◽  
G Protein Α Subunit

scholarly journals Repression of Adipogenesis by Adenylyl Cyclase Stimulatory G-protein α Subunit Is Expressed within Region 146-220

1996 ◽  
Vol 271 (36) ◽  
pp. 22022-22029 ◽  
Author(s):  
Hsien-yu Wang ◽  
Gary L. Johnson ◽  
Xunxian Liu ◽  
Craig C. Malbon
Keyword(s):  
Adenylyl Cyclase ◽  
G Protein ◽  
Α Subunit ◽  
Stimulatory G Protein ◽  
G Protein Α Subunit

scholarly journals Modulation of rat cardiac sodium channel by the stimulatory G protein α subunit

1999 ◽  
Vol 518 (2) ◽  
pp. 371-384 ◽  
Author(s):  
Tong Lu ◽  
Hon-Chi Lee ◽  
Julia A. Kabat ◽  
Erwin F. Shibata
Keyword(s):  
Sodium Channel ◽  
G Protein ◽  
Α Subunit ◽  
Cardiac Sodium Channel ◽  
Stimulatory G Protein ◽  
G Protein Α Subunit

Genetic Variation of the Extra-large Stimulatory G Protein α-Subunit Leads to Gs Hyperfunction in Platelets and Is a Risk Factor for Bleeding

2001 ◽  
Vol 86 (09) ◽  
pp. 733-738 ◽  
Author(s):  
Kathleen Freson ◽  
Marc Hoylaerts ◽  
Jaak Jaeken ◽  
Marijke Eyssen ◽  
Jozef Arnout ◽  
...  
Keyword(s):  
G Protein ◽  
Control Group ◽  
Variable Degree ◽  
Bleeding Tendency ◽  
Functional Polymorphism ◽  
Α Subunit ◽  
Normal Platelet ◽  
Camp Generation ◽  
Stimulatory G Protein ◽  
G Protein Α Subunit

SummaryAlternatively spliced GNAS1 and XL-GNAS1, encoding respectively the stimulatory G-protein α-subunit (Gsα) and the extra-large stimulatory G-protein α-subunit (XLsα), are located on the imprinted chromosomal region 20q13.12-13. We presently report a functional polymorphism in the imprinted XL-GNAS1 gene. In three patients, a 36 bp insertion and two basepair substitutions flanking this insertion were found in the paternally inherited XL-GNAS1 exon 1. They clinically manifest an enhanced trauma-related bleeding tendency and a variable degree of mental retardation. A platelet aggregation inhibition test to evaluate Gs function was developed. Their platelets display Gs hyperfunction and an enhanced cAMP generation upon stimulation of Gs-coupled receptors. The prevalence of the XLsα insertion in a normal control group was 2.2%. Normal controls, inheriting the insertion maternally, had a normal platelet Gs activity, whereas controls inheriting the insertion paternally had increased inducible platelet Gs activity, defining the insertion as a functional polymorphism. This paternally inherited XLsα insertion represents a new genetic cause of an inherited bleeding tendency, although to a variable degree.

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