000			02662nab a2200289 a 4500
003			AR-ReUNN
005			20260702004755.0
008			260701s2023 ag |||||||||||||||||spa
100	1		_aShimomura-Kuroki, Junko _9199377
700	1		_aFarooq, Muhammad _9199378
700	1		_aSekimoto, Tsuneo _9199379
700	1		_aAmisuka, Norio _9199380
700	1		_aShimomura, Yukata _9199381
245	1	0	_aCharacterization of a PTH1R missense mutation responsible for Jansen type metaphyseal chondrodysplasia
264		1	_c2023
300			_a5 páginas
520			_aParathyroid hormone and parathyroid hormone-related peptide (PTHrP), and its receptor (PTH1R) play an important role in differentiation of bone and cartilage in the developing stages. Constitutive dimers of PTH1R are believed to be dissociated by ligand binding, and monomeric PTH1R is capable of activating G protein. Jansen type metaphyseal chondrodysplasia is caused by missense mutations in PTH1R, which are constitutively active even without the presence of the ligands. However, the underlying pathomechanisms remained largely unknown. In this study, we have attempted to further characterize a PTH1R missense mutation H223R responsible for Jansen type metaphyseal chondrodysplasia. cDNAs encoding wild-type (Wt)- and H223R mutant (Mut)-PTH1R were transfected into HEK293T cells, and as a consequence of western blots, both the Wt- and Mut-PTH1R proteins showed several fragments between 55 and 65 kDa in size, while the patterns of N-glycosylation were distinct between them. Then we hypothesized that the Mut-PTH1R might physically interact with the Wt-PTH1R, leading to affect the downstream cAMP accumulation. Co-immunoprecipitation assays clearly showed that interaction occurred not only between the Wt-PTH1R themselves, but also between the Wt- and Mut-PTH1R. Furthermore, we performed CRE reporter assays to investigate cAMP accumulation. Constitutive, ligand-independent cAMP accumulation was observed in HEK293T cells expressing the Mut-PTH1R. Interestingly, there was a statistically lower constitutive activity in HEK293T cells co-expressing the Wt- and Mut-PTH1R proteins. Summarizing, it seems likely that Mut-PTH1R may be, at least in part, co-localized with Wt-PTH1R by forming a heterodimer, leading to affect the function to each other.
650		4	_aDimerización _9199382
650		4	_aReceptor Acoplado a Proteina G _9199383
650		4	_aCondrodisplasia Metafisiaria Tipo Jansen _9199384
650		4	_aHpt _9199385
650		4	_aPth1r _9199386
773	0		_tOdontology _x1618-1247 _gv. 105 n. 2 (2017) _w257190
942			_cART
035			_a(ODN)65672
001			266516
999			_c266516 _d266516
040			_aAR-ReUNN _bspa _cAR-ReUNN _eaacr2