[Signal transduction of the thyrotropin receptor].
The thyrotropin receptor (TSHR) mediates dual signalling, cAMP and phosphoinositide (PIP2) responses. We have characterized the roles of the 2nd and 3rd cytoplasmic loops on signal transduction by site-directed mutagenesis. Middle portion in the 2nd loop (residues 525-527) is found to be important for Gs coupling. On the other hand, N- and C-terminal regions of the 3rd loop and residues 528-532 in the 2nd loop are important for Gq coupling. Further, mutations involving residue 617-620 in the 3rd loop result in constitutive activation. Constitutively activating mutations of the TSHR and LH/CGR (lutropin/choriogonadotropin receptor) are found in functional thyroid adenoma and familial male precocious puberty, respectively, and appear to be the direct cause of each disease.
Kosugi
S
S
Department of Laboratory Medicine, Kyoto University School of Medicine.
Mori
T
T
D000242:Cyclic AMP / Q000378:metabolism; D005260:Female; D006801:Humans; D007295:Inositol Phosphates / Q000378:metabolism; D008297:Male; D016297:Mutagenesis, Site-Directed; D011629:Puberty, Precocious / Q000209:etiology / Q000235:genetics; D011989:Receptors, Thyrotropin / Q000502:physiology*; D015398:Signal Transduction
D007295:Inositol Phosphates; D011989:Receptors, Thyrotropin; D000242:Cyclic AMP