PDGF-D is a specific, protease-activated ligand for the PDGF β-receptor
PDGF-D is a specific, protease-activated ligand for the PDGF β-receptor
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DOI：
10.1038/35074588
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发表时间：
2001-05-01
影响因子：
21.3
通讯作者：
Eriksson, U
中科院分区：
文献类型：
--
作者：
Bergsten, E;Uutela, M;Eriksson, U
血小板衍生生长因子(PDGF)是一种二硫键结合的二聚体异构体家族，对多种结缔组织细胞的生长、存活和功能具有重要作用。到目前为止，已经确定了三种不同的PDGF链--经典的PDGF-A和PDGF-B-1、B-2以及最近发现的PDGF-C-3。PDGF亚型(PDGF-AA、AB、BB和CC)通过与两种受体酪氨酸激酶的不同结合发挥其细胞效应。PDGFα受体(PDGFR-α)与所有三条PDGF链结合，而β-受体(PDGFR-β)仅与PDGF-B-1结合。用小鼠进行的基因靶向研究表明，PDGF-A和PDGF-B的基因以及这两个PDGFR基因对于正常发育是必不可少的。此外，PDGFs的过度表达与不同的病理条件有关，包括恶性肿瘤、动脉粥样硬化和纤维增生性疾病(1)。在这里，我们已经确定和表征了PDGF家族的第四个成员，PDGF-D。PDGF-D具有类似于PDGF-C-3的双域结构，以二硫键连接的同源二聚体PDGF-DD的形式分泌，当有限的蛋白降解时，PDGF-DD被激活，成为PDGFR-β的特异性激动型配体。PDGF-DD是第一个已知的PDGFR-β特异性配体，其独特的受体特异性表明它可能在几个器官的发育和病理生理学中起重要作用。
The term 'platelet-derived growth factor' (PDGF) refers to a family of disulphide-bonded dimeric isoforms that are important for growth, survival and function in several types of connective tissue cell. So far, three different PDGF chains have been identified - the classical PDGF-A and PDGF-B-1,B-2 and the recently identified PDGF-C-3. PDGF isoforms (PDGF-AA, AB, BB and CC) exert their cellular effects by differential binding to two receptor tyrosine kinases. The PDGF alpha -receptor (PDGFR-alpha) binds to all three PDGF chains, whereas the beta -receptor (PDGFR-beta) binds only to PDGF-B-1. Gene-targeting studies using mice have shown that the genes for PDGF-A and PDGF-B, as well as the two PDGFR genes, are essential for normal development(4). Furthermore, overexpression of PDGFs is linked to different pathological conditions, including malignancies, atherosclerosis and fibroproliferative diseases(1). Here we have identify and characterize a fourth member of the PDGF family, PDGF-D. PDGF-D has a two-domain structure similar to PDGF-C-3 and is secreted as a disulphide-linked homodimer, PDGF-DD, Upon limited proteolysis, PDGF-DD is activated and becomes a specific agonistic ligand for PDGFR-beta. PDGF-DD is the first known PDGFR-beta -specific ligand, and its unique receptor specificity indicates that it may be important for development and pathophysiology in several organs.