Shedding of Human Thyrotropin Receptor Ectodomain

Shedding of Human Thyrotropin Receptor Ectodomain
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人促甲状腺素受体胞外域的脱落

DOI:
10.1074/jbc.271.8.4545
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发表时间:
1996
期刊:
The Journal of Biological Chemistry
影响因子:
--
通讯作者:
M. Misrahi
M. Misrahi
中科院分区:
--
文献类型:
--
作者:
J. Couet;S. Sar;A. Jolivet;M. V. Hai;E. Milgrom;M. Misrahi

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人甲状腺中的促甲状腺激素(TSH)受体已被证明切割成一个细胞外α亚基和一个跨膜β亚基,通过二硫键连接在一起。相对于前者,后者组分的过量表明了胞外域的脱落。事实上,我们在人甲状腺细胞和永久转染的L或中国仓鼠卵巢细胞的培养物中观察到了这种脱落。通过内吞作用、再循环和溶酶体降解的抑制剂增加脱落,表明其依赖于细胞表面的受体驻留。TSH和佛波酯略有增加,而毛喉素和8-溴环AMP没有影响。降低细胞培养基中的血清浓度通过未知机制增强脱落。TSH受体α结构域的脱落是两个事件的结果:受体裂解为α和β亚基以及二硫键的还原。特异性抑制剂BB-2116对可溶性TSH受体脱落的完全抑制表明,裂解反应可能在细胞表面由基质金属蛋白酶催化。这种脱落机制可能是人体循环中可溶性TSH受体α亚单位存在的原因。
The thyrotropin (TSH) receptor in human thyroid glands has been shown to be cleaved into an extracellular α subunit and a transmembrane β subunit held together by disulfide bridges. An excess of the latter component relative to the former suggested the shedding of the ectodomain. Indeed we observed such a shedding in cultures of human thyrocytes and permanently transfected L or Chinese hamster ovary cells. The shedding was increased by inhibitors of endocytosis, recycling, and lysosomal degradation, suggesting that it was dependent on receptor residency at the cell surface. It was slightly increased by TSH and phorbol esters, whereas forskolin and 8-bromo-cyclic AMP were without effect. Decreasing the serum concentration in cell culture medium enhanced the shedding by an unknown mechanism. The shedding of the TSH receptor α domain is the consequence of two events: cleavage of the receptor into α and β subunits and reduction of the disulfide bridge(s). The complete inhibition of soluble TSH receptor shedding by the specific inhibitor BB-2116 indicated that the cleavage reaction is catalyzed probably at the cell surface by a matrix metalloprotease. This shedding mechanism may be responsible for the presence of soluble TSH receptor α subunit in human circulation.
DOI: --
发表时间: 1993
期刊: The Journal of biological chemistry
影响因子: --
作者:
Sires,UI;Griffin,GL;Broekelmann,TJ;Mecham,RP;Murphy,G;Chung,AE;Welgus,HG;Senior,RM
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促甲状腺素受体的裂解不会发生在经典的枯草杆菌蛋白酶相关的前蛋白转化酶内切蛋白水解位点。
DOI: --
发表时间: 1994
期刊: The Journal of biological chemistry
影响因子: --
作者:
Chazenbalk,GD;Rapoport,B
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DOI: 10.1016/s0021-9258(18)47322-x
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期刊: The Journal of biological chemistry
影响因子: --
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Deborah;Bravo;Julja B. GleasonSn;Rosa I. Sanchez;Richard;Rothll;Robert;Fuller
通讯作者: Deborah;Bravo;Julja B. GleasonSn;Rosa I. Sanchez;Richard;Rothll;Robert;Fuller
促甲状腺素 (TSH) 受体的新结构模型,通过 TSH 与完整细胞中重组受体的共价交联确定:单多肽链的证据。
DOI: 10.1210/mend-5-11-1607
发表时间: 1991
期刊: Molecular endocrinology (Baltimore, Md.)
影响因子: --
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通讯作者: Rapoport,B
DOI: 10.1210/mend-4-4-525
发表时间: 1990-04-01
影响因子: --
作者:
SPRENGEL, R;BRAUN, T;SEEBURG, PH
通讯作者: SEEBURG, PH