Gs alpha mutations in hyperfunctioning thyroid adenomas.
Hyperfunctioning thyroid adenomas are benign tumors characterized by their autonomous growth and functional activity, which frequently cause clinical hyperthyroidism and show a predominant radioactive iodine uptake in the nodule. Activating mutations in the gene encoding the alpha subunit of the stimulatory G protein (Gs alpha), as well as activating mutations in the gene encoding thyrotropin receptor in hyperfunctioning thyroid adenomas, have been reported. The mutations in Gs alpha involved the replacement of either arginine 201 with cysteine or histidine, or glutamine 227 with arginine or leucine. These residues are involved in GDP/GTP binding of Gs alpha and these mutations inhibit intrinsic GTPase activity that results in constitutive activation of adenylyl cyclase. The pathophysiological roles of these mutations in the formation of hyperfunctioning thyroid adenoma have been suggested.
Murakami
M
M
First Department of Internal Medicine, Gunma University School of Medicine, Maebashi, Japan. mmurakam@sb.gunma-u.ac.jp
Kamiya
Y
Y
Yanagita
Y
Y
Mori
M
M
D000236:Adenoma / Q000235:genetics* / Q000503:physiopathology*; D000818:Animals; D019205:GTP-Binding Protein alpha Subunits, Gs / Q000235:genetics*; D006801:Humans; D009154:Mutation; D015513:Oncogene Proteins / Q000235:genetics*; D013964:Thyroid Neoplasms / Q000235:genetics* / Q000503:physiopathology*
D015513:Oncogene Proteins; D019205:GTP-Binding Protein alpha Subunits, Gs