人类生长激素受体的短亚型作为全长受体的主要负性抑制剂，并产生大量的结合蛋白。
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Ross RJ, Esposito N, Shen XY, Von Laue S, Chew SL, Dobson PR, Postel-Vinay MC, Finidori J
人类生长激素受体的短亚型作为全长受体的主要负性抑制剂，并产生大量的结合蛋白。
分子内分泌。1997 3月11日(3):265-73。
- PubMed ID
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9058373 (PubMed视图］
- 摘要
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生长激素受体(GHR)是细胞因子受体家族的一员。由选择性剪接引起的短异构体已被报道为该家族中的许多蛋白质。在人肝脏和培养的IM-9细胞中，使用GHR外显子7和10的引物进行RT-PCR实验，揭示了三个反映GHR mRNA选择性剪接的条带:在453 bp的预测产物和在427和383 bp的另外两个产物。427 bp的产物(GHR1-279)利用了外显子9下游26 bp的另一个3'-受体剪接位点;预测的c端残基为6个帧移外显子9密码子，以帧内终止密码子结尾。383 bp的产物(GHR1-277)源于9号外显子的跳跃;预测的c端残基是3个帧移外显子10密码子，以帧内终止密码子结尾。RNase保护实验证实了GHR1-279变体在IM-9细胞和人类肝脏中的存在。GHR1-279的替代剪接占全长的比例为1-10%，GHR1-277的比例小于1%。在表达载体中亚克隆GHR1-279并瞬时转染293细胞后检测其功能。 Scatchard analysis of competition curves for [125l]-hGH bound to cells transfected either with GHR full length (GHRfl) or GHR1-279 revealed a 2-fold reduced affinity and 6-fold increased number of binding sites for GHR1-279. The increased expression of GHR1-279 was confirmed by cross-linking studies. The media of cells transfected with GHR1-279 contained 20-fold more GH-binding protein (GHBP) than that found in the media of cells transfected with the full-length receptor. Immunoprecipitation and Western blotting experiments, using a combination of antibodies directed against extracellular and intracellular GHR epitopes, demonstrated that GHRfl and GHR1-279 can form heterodimers and that the two forms also generate a 60-kDa GHBP similar in size to the GHBP in human serum. Functional tests using a reporter gene, containing Stat5-binding elements, confirmed that while the variant form was inactive by itself, it could inhibit the function of the full-length receptor. We have demonstrated the presence of a splice variant of the GHR in human liver encoding a short form of the receptor similar in size to a protein previously identified in human liver and choroid plexus. Expression studies in 293 cells support the hypothesis that while the expression of the splice variant accounts for only a small proportion of the total GHR transcript, it produces a short isoform that modulates the function of the full-length receptor, inhibits signaling, and generates large amounts of GHBP. The differential expression of GHR receptor short forms may regulate the production of GHBP, and truncated receptors may act as transport proteins or negative regulators of GHR signaling.