Direct interaction of the extracellular matrix protein DANCE with apolipoprotein(a) mediated by the kringle IV-type 2 domain
Direct interaction of the extracellular matrix protein DANCE with apolipoprotein(a) mediated by the kringle IV-type 2 domain
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DOI：
10.1007/s00438-002-0673-6
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发表时间：
2002-06-01
影响因子：
3.1
通讯作者：
Utermann, G
中科院分区：
文献类型：
--
作者：
Kapetanopoulos, A;Fresser, F;Utermann, G
脂蛋白（a）[Lp（a）]由LDL和载脂蛋白（a）组成。并且已经被证明是一个独立的，主要的。动脉硬化和血栓形成的危险因素。进一步阐明Lp（a）/apo（a）的病理生理功能。我们寻找新的蛋白质配体。使用酵母双杂交系统并使用来自apo（a）的高度重复的kringle IV 2型（KIV-2）序列作为诱饵。细胞外基质蛋白DANCE [发育动脉和神经嵴表皮生长因子（EGF）样]最近被确定为动脉粥样硬化发生的相互作用。DANCE和载脂蛋白（a）之间的直接物理相互作用通过共纯化来自瞬时转染COS-1细胞培养上清液的两种重组蛋白来证实。此外，还观察到人血浆衍生的Lp（a）与重组DANCE的结合。最后，当将单克隆抗apo（a）和多克隆抗DANCE抗体应用于动脉粥样硬化颈动脉的组织切片时，发现这两种蛋白质共定位于内皮细胞和平滑肌细胞中，表明它们一起出现在动脉壁中。然而，到目前为止，这种新发现的DANCE：Lp（a）apo（a）相互作用的体内相关性和可能的功能作用仍然是推测性的。
Lipoprotein(a) [Lp(a)] consists of LDL and apolipoprotein(a). and has been shown to be a major, independent. risk factor for arteriosclerosis and thrombosis in humans. To further elucidate the (patho)physiological function(s) of Lp(a)/apo(a). we searched for new protein ligands. using the yeast two-hybrid system and employing the highly repetitive kringle IV type 2 (KIV-2) sequence from apo(a) as bait. The extracellular matrix protein DANCE [developmental arteries and neural crest epidermal growth factor (EGF)-like] recently implicated in atherogenesis was identified as an interactor. A direct physical interaction between DANCE and apo(a) was confirmed by co-purification of both recombinant proteins derived from culture supernatants of transiently transfected COS-1 cells. Furthermore, binding of human, plasma-derived Lp(a) to recombinant DANCE was also observed. Finally, when monoclonal anti-apo(a) and polyclonal anti-DANCE antibodies were applied to tissue slices of atherosclerotic carotid artery, the two proteins were found to be co-localized in endothelial and smooth muscle cells, suggesting that they occur together in the arterial wall. However, as yet, the in vivo relevance and the possible functional role of this newly identified DANCE:Lp(a) apo(a) interaction remains speculative.