Augmented binding and activation of latent transforming growth factor-beta by a tryptic fragment of latency associated peptide.
Augmented binding and activation of latent transforming growth factor-beta by a tryptic fragment of latency associated peptide.
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通过潜伏相关肽的胰蛋白酶片段增强潜伏转化生长因子-β 的结合和激活。
DOI：
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发表时间：
2002
期刊：
影响因子：
--
通讯作者：
Motoo Yamasaki
中科院分区：
文献类型：
--
作者：
M. Abe;Nobuyuki Oda;Y. Sato;K. Shibata;Motoo Yamasaki
转化生长因子-β（TGF-β）以潜伏形式分泌;因此，活化对于控制TGF-β作用至关重要。潜伏性TGF-β存在于一种复合物中，其中成熟TGF-β与潜伏相关肽（latency associated peptide，LTP）和潜伏性TGF-β结合蛋白（latent TGF-β binding protein，LTBP）复合物非共价连接。我们已经证明，在内皮细胞（EC）和平滑肌细胞（SMC）的异型培养物中，潜伏的TGF-β被有效激活。在这些条件下，TGF-β在将潜伏的TGF-β靶向SMC表面方面起着重要作用，纤溶酶和钙蛋白酶将其靶向EC表面进行活化。在这里，我们证明了在一个同型培养系统中，TGF-β的片段增加了潜在的TGF-β与内皮细胞的结合，导致其激活细胞相关的蛋白水解。TGF-β片段似乎与细胞表面结合，并增加潜伏TGF-β的结合，而不依赖于转氨酶。这些结果表明，一个独特的机制激活潜伏TGF-β的蛋白水解片段的TGF-β。该机制可能是由于在某些条件下蛋白酶水平升高引起的降解。
Transforming growth factor-beta (TGF-beta) is secreted in a latent form; thus, activation is critical for the control of TGF-beta action. Latent TGF-beta exists in a complex in which mature TGF-beta is noncovalently linked to latency associated peptide (LAP) and latent TGF-beta binding protein (LTBP) complex. We have shown that latent TGF-beta is efficiently activated in heterotypic cultures of endothelial cells (ECs) and smooth muscle cells (SMCs). Under those conditions, LAP plays an important role in targeting latent TGF-beta to the surface of SMCs, and plasmin and calpain target it to the surface of ECs for activation. Here, we demonstrate in a homotypic culture system that fragments of LAP increase the binding of latent TGF-beta to ECs, resulting in its activation by cell-associated proteolysis. LAP fragments appear to bind to the cell surface and augment the binding of latent TGF-beta, independent of transglutaminase. These results suggest a unique mechanism for the activation of latent TGF-beta by proteolytic fragments of LAP. The mechanism may arise from degradation by elevated levels of proteases under certain conditions.
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影响因子：
2.9
作者：
ABE, M;HARPEL, JG;RIFKIN, DB
通讯作者：
RIFKIN, DB
影响因子：
10.5
作者：
Q. Yu;I. Stamenkovic
通讯作者：
Q. Yu;I. Stamenkovic
影响因子：
15.9
作者：
Sankar, S;MahootiBrooks, N;Madri, JA
通讯作者：
Madri, JA
DOI：
10.1073/pnas.88.2.580
发表时间：
1991-01-01
影响因子：
11.1
作者：
DENNIS, PA;RIFKIN, DB
通讯作者：
RIFKIN, DB