help button home button Endocrine Society Molecular Endocrinology ENDO 08 Sessions Library
HOME HELP FEEDBACK SUBSCRIPTIONS ARCHIVE SEARCH TABLE OF CONTENTS
Molecular Endocrinology, doi:10.1210/me.2002-0054
This Article
Right arrow Full Text
Right arrow Full Text (PDF)
Right arrow Alert me when this article is cited
Right arrow Alert me if a correction is posted
Right arrow Citation Map
Services
Right arrow Email this article to a friend
Right arrow Similar articles in this journal
Right arrow Similar articles in PubMed
Right arrow Alert me to new issues of the journal
Right arrow Download to citation manager
Right arrow Request Copyright Permission
Citing Articles
Right arrow Citing Articles via HighWire
Right arrow Citing Articles via Google Scholar
Google Scholar
Right arrow Articles by Bastepe, M.
Right arrow Articles by Jüppner, H.
Right arrow Search for Related Content
PubMed
Right arrow PubMed Citation
Right arrow Articles by Bastepe, M.
Right arrow Articles by Jüppner, H.
Molecular Endocrinology 16 (8): 1912-1919
Copyright © 2002 by The Endocrine Society

Receptor-Mediated Adenylyl Cyclase Activation Through XL{alpha}s, the Extra-Large Variant of the Stimulatory G Protein {alpha}-Subunit

Murat Bastepe, Yasemin Gunes, Beatriz Perez-Villamil, Joy Hunzelman, Lee S. Weinstein and Harald Jüppner

Endocrine Unit (M.B., Y.G., J.H., H.J.) and Cancer Center (B.P.-V.), Massachusetts General Hospital and MassGeneral Hospital for Children (H.J.), and Harvard Medical School, Boston, Massachusetts 02114; Metabolic Diseases Branch (L.S.W.), National Institute of Diabetes, Digestive and Kidney Diseases, National Institutes of Health, Bethesda, Maryland 20892

Address all correspondence and requests for reprints to: Harald Jüppner, M.D., Endocrine Unit, Massachusetts General Hospital, 50 Blossom Street, WEL 5, Boston, Massachusetts 02114. E-mail: jueppner{at}helix.mgh.harvard.edu.

XL{alpha}s, the large variant of the stimulatory G protein {alpha} subunit (Gs{alpha}), is derived from GNAS1 through the use of an alternative first exon and promoter. Gs{alpha} and XL{alpha}s have distinct amino-terminal domains, but are identical over the carboxyl-terminal portion encoded by exons 2–13. XL{alpha}s can mimic some functions of Gs{alpha}, including ß{gamma} interaction and adenylyl cyclase stimulation. However, previous attempts to demonstrate coupling of XL{alpha}s 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 XL{alpha}s and Gs{alpha} (GnasE2-/E2-). GnasE2-/E2- cells transfected with plasmids encoding XL{alpha}s and different heptahelical receptors, including the ß2-adrenergic receptor and receptors for PTH, TSH, and CRF, showed agonist-mediated cAMP accumulation that was indistinguishable from that observed with cells transiently coexpressing Gs{alpha} and these receptors. Our findings thus indicate that XL{alpha}s is capable of functionally coupling to receptors that normally act via Gs{alpha}.




This article has been cited by other articles:


Home page
 EndocrinologyHome page
C. Aydin, N. Aytan, M. J. Mahon, H. A. W. Tawfeek, N. W. Kowall, A. Dedeoglu, and M. Bastepe
Extralarge XL{alpha}s (XXL{alpha}s), a Variant of Stimulatory G Protein {alpha}-Subunit (Gs{alpha}), Is a Distinct, Membrane-Anchored GNAS Product that Can Mimic Gs{alpha}
Endocrinology, August 1, 2009; 150(8): 3567 - 3575.
[Abstract] [Full Text] [PDF]

Home page
 J. Pharmacol. Exp. Ther.Home page
A. I. Kaya, O. Ugur, S. S. Oner, M. Bastepe, and H. O. Onaran
Coupling of {beta}2-Adrenoceptors to XL{alpha}s and G{alpha}s: A New Insight into Ligand-Induced G Protein Activation
J. Pharmacol. Exp. Ther., April 1, 2009; 329(1): 350 - 359.
[Abstract] [Full Text] [PDF]

Home page
 J. Clin. Endocrinol. Metab.Home page
K. Freson, B. Izzi, V. Labarque, M. Van Helvoirt, C. Thys, C. Wittevrongel, M. Bex, R. Bouillon, N. Godefroid, W. Proesmans, et al.
GNAS Defects Identified by Stimulatory G Protein {alpha}-Subunit Signalling Studies in Platelets
J. Clin. Endocrinol. Metab., December 1, 2008; 93(12): 4851 - 4859.
[Abstract] [Full Text] [PDF]

Home page
 Mol Biol EvolHome page
S. Wadhawan, B. Dickins, and A. Nekrutenko
Wheels within Wheels: Clues to the Evolution of the Gnas and Gnal Loci
Mol. Biol. Evol., December 1, 2008; 25(12): 2745 - 2757.
[Abstract] [Full Text] [PDF]

Home page
 PhysiologyHome page
S. Krechowec and A. Plagge
Physiological Dysfunctions Associated with Mutations of the Imprinted Gnas Locus
Physiology, August 1, 2008; 23(4): 221 - 229.
[Abstract] [Full Text] [PDF]

Home page
 J. Clin. Endocrinol. Metab.Home page
V. Mariot, S. Maupetit-Mehouas, C. Sinding, M.-L. Kottler, and A. Linglart
A Maternal Epimutation of GNAS Leads to Albright Osteodystrophy and Parathyroid Hormone Resistance
J. Clin. Endocrinol. Metab., March 1, 2008; 93(3): 661 - 665.
[Abstract] [Full Text] [PDF]

Home page
 Physiol. GenomicsHome page
A. Safdar, N. J. Yardley, R. Snow, S. Melov, and M. A. Tarnopolsky
Global and targeted gene expression and protein content in skeletal muscle of young men following short-term creatine monohydrate supplementation
Physiol Genomics, January 17, 2008; 32(2): 219 - 228.
[Abstract] [Full Text] [PDF]

Home page
 Hum Mol GenetHome page
S. Michienzi, N. Cherman, K. Holmbeck, A. Funari, M. T. Collins, P. Bianco, P. G. Robey, and M. Riminucci
GNAS transcripts in skeletal progenitors: evidence for random asymmetric allelic expression of Gs{alpha}
Hum. Mol. Genet., August 15, 2007; 16(16): 1921 - 1930.
[Abstract] [Full Text] [PDF]

Home page
 J. Biol. Chem.Home page
T. Xie, A. Plagge, O. Gavrilova, S. Pack, W. Jou, E. W. Lai, M. Frontera, G. Kelsey, and L. S. Weinstein
The Alternative Stimulatory G Protein {alpha}-Subunit XL{alpha}s Is a Critical Regulator of Energy and Glucose Metabolism and Sympathetic Nerve Activity in Adult Mice
J. Biol. Chem., July 14, 2006; 281(28): 18989 - 18999.
[Abstract] [Full Text] [PDF]

Home page
 Endocr. Rev.Home page
E. W. Hillhouse and D. K. Grammatopoulos
The Molecular Mechanisms Underlying the Regulation of the Biological Activity of Corticotropin-Releasing Hormone Receptors: Implications for Physiology and Pathophysiology
Endocr. Rev., May 1, 2006; 27(3): 260 - 286.
[Abstract] [Full Text] [PDF]

Home page
 EndocrinologyHome page
A. Linglart, M. J. Mahon, M. A. Kerachian, D. M. Berlach, G. N. Hendy, H. Juppner, and M. Bastepe
Coding GNAS Mutations Leading to Hormone Resistance Impair in Vitro Agonist- and Cholera Toxin-Induced Adenosine Cyclic 3',5'-Monophosphate Formation Mediated by Human XL{alpha}s
Endocrinology, May 1, 2006; 147(5): 2253 - 2262.
[Abstract] [Full Text] [PDF]

Home page
 Mol. Endocrinol.Home page
T. Dean, A. Linglart, M. J. Mahon, M. Bastepe, H. Juppner, J. T. Potts Jr., and T. J. Gardella
Mechanisms of Ligand Binding to the Parathyroid Hormone (PTH)/PTH-Related Protein Receptor: Selectivity of a Modified PTH(1-15) Radioligand for G{alpha}S-Coupled Receptor Conformations
Mol. Endocrinol., April 1, 2006; 20(4): 931 - 943.
[Abstract] [Full Text] [PDF]

Home page
 J. Biol. Chem.Home page
S. K. Shenoy, M. T. Drake, C. D. Nelson, D. A. Houtz, K. Xiao, S. Madabushi, E. Reiter, R. T. Premont, O. Lichtarge, and R. J. Lefkowitz
beta-Arrestin-dependent, G Protein-independent ERK1/2 Activation by the beta2 Adrenergic Receptor
J. Biol. Chem., January 13, 2006; 281(2): 1261 - 1273.
[Abstract] [Full Text] [PDF]

Home page
 IBMS BoneKEyHome page
M. Bastepe and H. Juppner
Pseudohypoparathyroidism, Gs{alpha}, and the GNAS Locus
IBMS BoneKEy, December 1, 2005; 2(12): 20 - 32.
[Full Text] [PDF]

Home page
 Physiol. Rev.Home page
N. Wettschureck and S. Offermanns
Mammalian G Proteins and Their Cell Type Specific Functions
Physiol Rev, October 1, 2005; 85(4): 1159 - 1204.
[Abstract] [Full Text] [PDF]

Home page
 Proc. Natl. Acad. Sci. USAHome page
M. Chen, O. Gavrilova, J. Liu, T. Xie, C. Deng, A. T. Nguyen, L. M. Nackers, J. Lorenzo, L. Shen, and L. S. Weinstein
Alternative Gnas gene products have opposite effects on glucose and lipid metabolism
PNAS, May 17, 2005; 102(20): 7386 - 7391.
[Abstract] [Full Text] [PDF]

Home page
 EndocrinologyHome page
L. S. Weinstein, J. Liu, A. Sakamoto, T. Xie, and M. Chen
Minireview: GNAS: Normal and Abnormal Functions
Endocrinology, December 1, 2004; 145(12): 5459 - 5464.
[Abstract] [Full Text] [PDF]

Home page
 Mol. Pharmacol.Home page
T. A. Vortherms, C. H. Nguyen, C. H. Berlot, and V. J. Watts
Using Molecular Tools to Dissect the Role of G{alpha}s in Sensitization of AC1
Mol. Pharmacol., December 1, 2004; 66(6): 1617 - 1624.
[Abstract] [Full Text] [PDF]

Home page
 Proc. Natl. Acad. Sci. USAHome page
M. Bastepe, L. S. Weinstein, N. Ogata, H. Kawaguchi, H. Juppner, H. M. Kronenberg, and U.-i. Chung
Stimulatory G protein directly regulates hypertrophic differentiation of growth plate cartilage in vivo
PNAS, October 12, 2004; 101(41): 14794 - 14799.
[Abstract] [Full Text] [PDF]

Home page
 EndocrinologyHome page
M. Chen, M. Haluzik, N. J. Wolf, J. Lorenzo, K. R. Dietz, M. L. Reitman, and L. S. Weinstein
Increased Insulin Sensitivity in Paternal Gnas Knockout Mice Is Associated with Increased Lipid Clearance
Endocrinology, September 1, 2004; 145(9): 4094 - 4102.
[Abstract] [Full Text] [PDF]

Home page
 J. Clin. Endocrinol. Metab.Home page
M. Bastepe and H. Juppner
Pseudohypoparathyroidism and Mechanisms of Resistance toward Multiple Hormones: Molecular Evidence to Clinical Presentation
J. Clin. Endocrinol. Metab., September 1, 2003; 88(9): 4055 - 4058.
[Full Text] [PDF]

Home page
 J. Clin. Endocrinol. Metab.Home page
E. L. Germain-Lee, J. Groman, J. L. Crane, S. M. Jan de Beur, and M. A. Levine
Growth Hormone Deficiency in Pseudohypoparathyroidism Type 1a: Another Manifestation of Multihormone Resistance
J. Clin. Endocrinol. Metab., September 1, 2003; 88(9): 4059 - 4069.
[Abstract] [Full Text] [PDF]

Home page
 J. Clin. Endocrinol. Metab.Home page
J. Liu, B. Erlichman, and L. S. Weinstein
The Stimulatory G Protein {alpha}-Subunit Gs{alpha} Is Imprinted in Human Thyroid Glands: Implications for Thyroid Function in Pseudohypoparathyroidism Types 1A and 1B
J. Clin. Endocrinol. Metab., September 1, 2003; 88(9): 4336 - 4341.
[Abstract] [Full Text] [PDF]

Home page
 Hum Mol GenetHome page
K. Freson, J. Jaeken, M. Van Helvoirt, F. de Zegher, C. Wittevrongel, C. Thys, M. F. Hoylaerts, J. Vermylen, and C. Van Geet
Functional polymorphisms in the paternally expressed XL{alpha}s and its cofactor ALEX decrease their mutual interaction and enhance receptor-mediated cAMP formation
Hum. Mol. Genet., May 15, 2003; 12(10): 1121 - 1130.
[Abstract] [Full Text] [PDF]


HOME HELP FEEDBACK SUBSCRIPTIONS ARCHIVE SEARCH TABLE OF CONTENTS
Endocrinology Endocrine Reviews J. Clin. End. & Metab.
Molecular Endocrinology Recent Prog. Horm. Res. All Endocrine Journals
Copyright © 2002 by The Endocrine Society