Plasminogen is tethered with high affinity to the cell surface by the plasma protein, histidine-rich glycoprotein
Plasminogen is tethered with high affinity to the cell surface by the plasma protein, histidine-rich glycoprotein
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DOI：
10.1074/jbc.m406027200
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发表时间：
2004-09-10
影响因子：
4.8
通讯作者：
Parish, CR
中科院分区：
文献类型：
--
作者：
Jones, AL;Hulett, MD;Parish, CR
纤溶酶原参与了入侵细胞对细胞外基质的降解，但目前尚未发现其高亲和力的细胞表面受体。先前的研究报道了血浆蛋白，富组氨酸糖蛋白（HRG），与纤溶酶原和细胞表面相互作用，提出了HRG可能将纤溶酶原/纤溶酶固定在细胞表面的可能性。在这里，我们显示，基于光学生物传感器分析，固定化HRG与可溶性纤溶酶原具有高亲和力和极慢的解离速率相互作用。此外，HRG-纤溶酶原相互作用是赖氨酸可解离的，主要涉及HRG的氨基末端结构域和纤溶酶原的第五kringle结构域，而不涉及HRG的羧基末端赖氨酸。HRG也被证明可以将纤溶酶原拴在细胞表面，这种相互作用在Zn2+水平升高和低pH值的情况下被增强，这种情况普遍存在于组织损伤、肿瘤生长和血管生成的部位。基于这些数据，我们提出HRG作为一种可溶性的接头分子，在组织损伤、肿瘤生长和血管生成的部位与细胞结合，提供一种高亲和力的受体，将纤溶酶原拴在细胞表面，从而增强细胞的迁移潜力。
Plasminogen has been implicated in extracellular matrix degradation by invading cells, but few high affinity cell surface receptors for the molecule have been identified. Previous studies have reported that the plasma protein, histidine-rich glycoprotein (HRG), interacts with plasminogen and cell surfaces, raising the possibility that HRG may immobilize plasminogen/plasmin to cell surfaces. Here we show, based on optical biosensor analyses, that immobilized HRG interacts with soluble plasminogen with high affinity and with an extremely slow dissociation rate. Furthermore, the HRG-plasminogen interaction is lysine-dissociable and involves predominately the amino-terminal domain of HRG, and the fifth kringle domain of plasminogen, but not the carboxyl-terminal lysine of HRG. HRG was also shown to tether plasminogen to cell surfaces, with this interaction being potentiated by elevated Zn2+ levels and low pH, conditions that prevail at sites of tissue injury, tumor growth, and angiogenesis. Based on these data we propose that HRG acts as a soluble adaptor molecule that binds to cells at sites of tissue injury, tumor growth, and angiogenesis, providing a high affinity receptor for tethering plasminogen to the cell surface and thereby enhancing the migratory potential of cells.