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Science 10 August 1990:
Vol. 249. no. 4969, pp. 655 - 659
DOI: 10.1126/science.2116665
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Articles

Science, Vol 249, Issue 4969, 655-659
Copyright © 1990 by American Association for the Advancement of Science

articles

Two G protein oncogenes in human endocrine tumors

J Lyons, CA Landis, G Harsh, L Vallar, K Grunewald, H Feichtinger, QY Duh, OH Clark, E Kawasaki, HR Bourne, and al. et

Department of Human Genetics, Cetus Corporation, Emeryville CA 94608.

Somatic mutations in a subset of growth hormone (GH)-secreting pituitary tumors convert the gene for the alpha polypeptide chain (alpha s) of Gs into a putative oncogene, termed gsp. These mutations, which activate alpha s by inhibiting its guanosine triphosphatase (GTPase) activity, are found in codons for either of two amino acids, each of which is completely conserved in all known G protein alpha chains. The likelihood that similar mutations would activate other G proteins prompted a survey of human tumors for mutations that replace either of these two amino acids in other G protein alpha chain genes. The first gene so far tested, which encodes the alpha chain of Gi2, showed mutations that replaced arginine-179 with either cysteine or histidine in 3 of 11 tumors of the adrenal cortex and 3 of 10 endocrine tumors of the ovary. The mutant alpha i2 gene is a putative oncogene, referred to as gip2. In addition, gsp mutations were found in 18 of 42 GH-secreting pituitary tumors and in an autonomously functioning thyroid adenoma. These findings suggest that human tumors may harbor oncogenic mutations in various G protein alpha chain genes.


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J. Clin. Endocrinol. Metab. 83, 130-134
   Abstract »    Full Text »
No Evidence of a Role for Mutations or Polymorphisms of the Follicle-Stimulating Hormone Receptor in Ovarian Granulosa Cell Tumors.
P. J. Fuller, K. Verity, Y. Shen, P. Mamers, T. Jobling, and H. G. Burger (1998)
J. Clin. Endocrinol. Metab. 83, 274-279
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Crystal Structure of the Adenylyl Cyclase Activator Gsalpha .
R. K. Sunahara, J. J. Tesmer, A. G. Gilman, and S. R. Sprang (1997)
Science 278, 1943-1947
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The Thyrotropin Receptor in Thyroid Diseases.
R. Paschke and M. Ludgate (1997)
N. Engl. J. Med. 337, 1675-1681
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A Novel Transcript for the Thyrotropin-Releasing Hormone Receptor in Human Pituitary and Pituitary Tumors.
M. Yamada, K. Hashimoto, T. Satoh, N. Shibusawa, H. Kohga, Y. Ozawa, S. Yamada, and M. Mori (1997)
J. Clin. Endocrinol. Metab. 82, 4224-4228
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Somatic Mutations in the Thyrotropin Receptor Gene and Not in the Gs{alpha} Protein Gene in 31 Toxic Thyroid Nodules.
D. Fuhrer, H.-P. Holzapfel, P. Wonerow, W. A. Scherbaum, and R. Paschke (1997)
J. Clin. Endocrinol. Metab. 82, 3885-3891
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Platelet-activating Factor (PAF) Induces Growth Stimulation, Inhibition, and Suppression of Oncogenic Transformation in NRK Cells Overexpressing the PAF Receptor.
K. Kume and T. Shimizu (1997)
J. Biol. Chem. 272, 22898-22904
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Deletion of the Adrenocorticotropin Receptor Gene in Human Adrenocortical Tumors: Implications for Tumorigenesis.
M. Reincke, P. Mora, F. Beuschlein, W. Arlt, G. P. Chrousos, and B. Allolio (1997)
J. Clin. Endocrinol. Metab. 82, 3054-3058
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Structural and Functional Abnormalities at 11p15 Are Associated with the Malignant Phenotype in Sporadic Adrenocortical Tumors: Study on a Series of 82 Tumors.
C. Gicquel, M.-L. Raffin-Sanson, V. Gaston, X. Bertagna, P.-F. Plouin, M. Schlumberger, A. Louvel, J.-P. Luton, and Y. Le Bouc (1997)
J. Clin. Endocrinol. Metab. 82, 2559-2565
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Diversity and Prevalence of Somatic Mutations in the Thyrotropin Receptor and Gs{alpha} Genes as a Cause of Toxic Thyroid Adenomas.
J. Parma, L. Duprez, J. Van Sande, J. Hermans, P. Rocmans, G. Van Vliet, S. Costagliola, P. Rodien, J. E. Dumont, and G. Vassart (1997)
J. Clin. Endocrinol. Metab. 82, 2695-2701
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Thyroid-Specific Expression of Cholera Toxin A1 Subunit Causes Thyroid Hyperplasia and Hyperthyroidism in Transgenic Mice.
M. A. Zeiger, M. Saji, Y. Gusev, W. H. Westra, Y. Takiyama, W. C. Dooley, L. D. Kohn, and M. A. Levine (1997)
Endocrinology 138, 3133-3140
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The p53 tumor suppressor targets a novel regulator of G protein signaling.
L. Buckbinder, S. Velasco-Miguel, Y. Chen, N. Xu, R. Talbott, L. Gelbert, J. Gao, B. R. Seizinger, J. S. Gutkind, and N. Kley (1997)
PNAS 94, 7868-7872
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Ablation of Go alpha -Subunit Results in a Transformed Phenotype and Constitutively Active Phosphatidylcholine-specific Phospholipase C.
J. Cheng, J. D. Weber, J. J. Baldassare, and D. M. Raben (1997)
J. Biol. Chem. 272, 17312-17319
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An activating mutation in a Caenorhabditis elegans Gs protein induces neural degeneration..
H C Korswagen, J H Park, Y Ohshima, and R H Plasterk (1997)
Genes & Dev. 11, 1493-1503
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Activation of the Calcium-permeable Cation Channel CD20 by alpha  Subunits of the Gi Protein.
M. Kanzaki, M. A. Lindorfer, J. C. Garrison, and I. Kojima (1997)
J. Biol. Chem. 272, 14733-14739
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Somatostatin Acts by Inhibiting the Cyclic 3',5'-Adenosine Monophosphate (cAMP)/Protein Kinase A Pathway, cAMP Response Element-Binding Protein (CREB) Phosphorylation, and CREB Transcription Potency.
J. J. Tentler, J. R. Hadcock, and A. Gutierrez-Hartmann (1997)
Mol. Endocrinol. 11, 859-866
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Pituitary Tumor Pathogenesis.
I. Shimon and S. Melmed (1997)
J. Clin. Endocrinol. Metab. 82, 1675-1681
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