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001-es BibID:BIBFORM003461
Első szerző:Kaczur Viktória
Cím:Cleavage of the human thyrotropin receptor by ADAM10 is regulated by thyrotropin / Viktoria Kaczur, Laszló G. Puskas, Zsuzsanna U. Nagy, Nabil Miled, Ahmed Rebai, Ferenc Juhasz, Zoltan Kupihar, Agnes Zvara, Laszlo Hackler Jr., Nadir R. Farid
Megjegyzések:The thyrotropin receptor (TSHR) has a unique 50 residue (317-366) ectodomain insertion that sets it apart from other glycoprotein hormone receptors (GPHRs). Other ancient members of the leucine-rich repeat G protein-coupled receptor (GPCR) (LGR) family do exhibit ectodomain insertions of variable lengths and sequences. The TSHR-specific insert is digested, apparently spontaneously, to release the ectodomain (A-subunit) leaving the balance of the ectodomain attached to the serpentine (B-subunit). Despite concerted efforts for the last 12 years by many laboratories, the enzyme involved in TSHR cleavage has not been identified and a physiologic role for this process remains unclear. Several lines of evidence had suggested that the TSHR protease is likely a member of the a disintegrin and metalloprotease (ADAM) family of metalloproteases. We show here that the expression of ADAM10 was specific to the thyroid by specially designed DNA microarrays. We also show that TSH increases TSHR cleavage in a dose-dependent manner. To prove that ADAM10 is indeed the TSHR cleavage enzyme, we investigated the effect of TSH-induced cleavage by a peptide based on a motif (TSHR residues 334-349), shared with known ADAM10 substrates. TSH increased dose dependently TSHR ectodomain cleavage in the presence of wild-type peptide but not a scrambled control peptide. Interestingly, TSH increased the abundance of non-cleaved single chain receptor, as well higher molecular forms of the A-subunit, despite their enhancement of the appearance of the fully digested A-subunit. This TSH-related increase in TSHR digested forms was further increased by wild-type peptide. We have identified for the first time ADAM10 as the TSHR cleavage enzyme and shown that TSH regulates its activation.
Tárgyszavak:Orvostudományok Klinikai orvostudományok idegen nyelvű folyóiratközlemény külföldi lapban
thyrotropin receptor, 50 residue insertion, A-subunit, DNA microarray, cleavage enzyme, ADAM10, TSHR substrate peptide
Megjelenés:Journal of Molecular Recognition. - 20 : 5 (2007), p. 392-404. -
További szerzők:Puskás László G. Nagy Zsuzsanna U. Miled, Nabil Rebai, Ahmed Kupihar Zoltán Zvara Ágnes Hackler László Jr. Farid, Nadir R. Juhász Ferenc (1952-) (sebész)
Internet cím:elektronikus változat
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