CaltechAUTHORS
  A Caltech Library Service

The human thyrotropin receptor: A heptahelical receptor capable of stimulating members of all four G protein families

Laugwitz, Karl-Ludwig and Allgeier, Anouk and Offermanns, Stefan and Spicher, Karsten and van Sande, Jackeline and Dumont, Jacques E. and Schultz, Günter (1996) The human thyrotropin receptor: A heptahelical receptor capable of stimulating members of all four G protein families. Proceedings of the National Academy of Sciences of the United States of America, 93 (1). pp. 116-120. ISSN 0027-8424. http://resolver.caltech.edu/CaltechAUTHORS:20141204-110722139

[img]
Preview
PDF - Published Version
See Usage Policy.

1566Kb

Use this Persistent URL to link to this item: http://resolver.caltech.edu/CaltechAUTHORS:20141204-110722139

Abstract

Thyrotropin is the primary hormone that, via one heptahelical receptor, regulates thyroid cell functions such as secretion, specific gene expression, and growth. In human thyroid, thyrotropin receptor activation leads to stimulation of the adenylyl cyclase and phospholipase C cascades. However, the G proteins involved in thyrotropin receptor action have been only partially defined. In membranes of human thyroid gland, we immunologically identified ɑ subunits of the G proteins G_(s short), G_(s long), Gi_(11), Gi_(12), Gi_(13), G_o (G_(o2) and another form of G_o, presumably G_(o1)), G_q, G_(11), G_(12), and G_(13). Activation of the thyrotropin (TSH) receptor by bovine TSH led to increased incorporation of the photoreactive GTP analogue [ɑ^(-32)P]GTP azidoanilide into immunoprecipitated alpha subunits of all G proteins detected in thyroid membranes. This effect was receptor-dependent and not due to direct G protein stimulation because it was mimicked by TSH receptor-stimulating antibodies of patients suffering from Grave disease and was abolished by a receptor-blocking antiserum from a patient with autoimmune hypothyroidism. The TSH-induced activation of individual G proteins occurred with EC_(50) values of 5-50 milliunits/ml, indicating that the activated TSH receptor coupled with similar potency to different G proteins. When human thyroid slices were pretreated with pertussis toxin, the TSH receptor-mediated accumulation of cAMP increased by approximately ≈ 35% with TSH at 1 milliunits/ml, indicating that the TSH receptor coupled to G_s and G_i. Taken together, these findings show that, at least in human thyroid membranes, in which the protein is expressed at its physiological levels, the TSH receptor resembles a naturally occurring example of a general G protein-activating receptor.


Item Type:Article
Related URLs:
URLURL TypeDescription
http://www.pnas.org/content/93/1/116PublisherArticle
http://dx.doi.org/10.1073/pnas.93.1.116DOIArticle
Additional Information:© 1996 National Academy of Sciences. Communicated by Henry R. Bourne, University of California, San Francisco, CA, August 28, 1995 (received for review February 14, 1995). We thank Evelyn Bombien for expert technical assistance, Drs. M. Ludgate and S. Costagliola for providing the high-activity TSH receptor-stimulating and TSH receptor-blocking immunoglobulins, and Drs. Th. Gudermann and B. Nürnberg for critical discussion of the manuscript. This work was supported by the Deutsche Forschungsgemeinschaft, Fonds der Chemischen Industrie, the Belgian Program on Interuniversity Poles of Attraction initiated by the Belgian State, Prime Minister's Office, Federal Service of Science, Technology and Culture, the Fonds National de la Recherche Scientifique (F.N.R.S.-Televie), and the Foundation Rose et Jean Hoguet.
Funders:
Funding AgencyGrant Number
Deutsche Forschungsgemeinschaft (DFG)UNSPECIFIED
Fonds der Chemischen IndustrieUNSPECIFIED
Belgian Program on Interuniversity Poles of Attraction initiated by the Belgian StateUNSPECIFIED
Fonds National de la Recherche Scientifique (F.N.R.S.-Televie)UNSPECIFIED
Foundation Rose et Jean HoguetUNSPECIFIED
Record Number:CaltechAUTHORS:20141204-110722139
Persistent URL:http://resolver.caltech.edu/CaltechAUTHORS:20141204-110722139
Official Citation:K L Laugwitz, A Allgeier, S Offermanns, K Spicher, J Van Sande, J E Dumont, and G Schultz The human thyrotropin receptor: a heptahelical receptor capable of stimulating members of all four G protein families PNAS 1996 93 (1) 116-120
Usage Policy:No commercial reproduction, distribution, display or performance rights in this work are provided.
ID Code:52384
Collection:CaltechAUTHORS
Deposited By: Ruth Sustaita
Deposited On:04 Dec 2014 20:13
Last Modified:04 Dec 2014 20:13

Repository Staff Only: item control page