Latent Transforming Growth Factor- (cid:1) (TGF- (cid:1) ) Binding Proteins: Orchestrators of TGF- (cid:1) Availability*
Latent Transforming Growth Factor- (cid:1) (TGF- (cid:1) ) Binding Proteins: Orchestrators of TGF- (cid:1) Availability*
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潜伏的转化生长因子-(Cid：1)(TGF-(Cid：1))1结合蛋白(LTBP-1-4)是一种分泌的多结构域糖蛋白，其中三个是调节转化生长因子-(Cid：1)的中心蛋白(1，2)。LTBP-1是潜伏的转化生长因子-1(CID：1)复合体的组成部分，它由转化生长因子-(CID：1)、转化生长因子-(CID：1)前肽和LTBP(图1)(3)组成。转化生长因子-1(CID：1)是以二聚体前蛋白的形式合成的，二聚体前肽是从生长因子(4)细胞内切割而来的。与大多数与成熟蛋白几乎没有亲和力的前肽不同，转化生长因子-1(CID：1)前肽与转化生长因子-1(CID：1)强烈结合，并且蛋白质以复合体(5)的形式分泌。在这个小的潜伏复合体(SLC)中，转化生长因子-1(CID：1)不能与其表面受体结合。因此，这种前肽被称为潜伏期相关蛋白(LAP)。从LAP解离或激活2是一个关键的调节事件，因为所有的转化生长因子-(CID：1)都是以潜伏的形式分泌的。LAP二聚体通常与第二个基因产物LTBP结合，三分子聚集体被称为大潜伏复合体(LLC)。
The latent transforming growth factor- (cid:1) (TGF- (cid:1) ) 1 binding pro- teins (LTBP-1–4) are secreted multidomain glycoproteins, three of which are central to TGF- (cid:1) regulation (1, 2). LTBP-1 is a compo- nent of the latent TGF- (cid:1) complex that consists of TGF- (cid:1) , the TGF- (cid:1) propeptide, and LTBP (Fig. 1) (3). TGF- (cid:1) is synthesized as a ho- modimeric proprotein, and the dimeric propeptide is cleaved intra-cellularly from the growth factor (4). Unlike most propeptides that have little affinity for the mature protein, the TGF- (cid:1) propeptide strongly binds to TGF- (cid:1) , and the proteins are secreted in complex (5). In this small latent complex (SLC), TGF- (cid:1) cannot bind to its surface receptors. Therefore, the propeptide is called the latency- associated protein (LAP). The dissociation or activation 2 of TGF- (cid:1) from LAP is a critical regulatory event as all TGF- (cid:1) is secreted in a latent form. The LAP dimer is usually disulfide-bound to a second gene product, LTBP, and the trimolecular aggregate is called the large latent complex (LLC).