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

• DOI: 10.1073/pnas.93.1.116
• Publication Date: 2002-07-26T14:35:50Z
• Authors: K L Laugwitz; A Allgeier; S Offermanns; K Spicher; J Van Sande; J E Dumont; G Schultz
• Keywords: Thyrotropin receptor; GTP-binding protein regulators; Thyrotropin-releasing hormone receptor

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 adenylyl cyclase phospholipase C cascades. However, G proteins involved in action have been only partially defined. membranes gland, we immunologically identified alpha subunits Gs short, long, Gi1, Gi2, Gi3, G(o) (Go2 another form Go, presumably Go1), Gq, G11, G12, G13. Activation (TSH) by bovine TSH led increased incorporation photoreactive GTP analogue [alpha-32P]GTP azidoanilide into immunoprecipitated all detected membranes. This effect was receptor-dependent not due direct protein because it mimicked receptor-stimulating antibodies patients suffering from Grave disease abolished a receptor-blocking antiserum patient with autoimmune hypothyroidism. The TSH-induced individual occurred EC50 values 5-50 milliunits/ml, indicating that activated coupled similar potency different proteins. When slices were pretreated pertussis toxin, receptor-mediated accumulation cAMP approximately 35% at 1 G(i). Taken together, these findings show least membranes, which expressed its physiological levels, resembles naturally occurring example general protein-activating receptor.