Wang X Q, Frazier W A
Department of Biochemistry and Molecular Biophysics, Washington University School of Medicine, St. Louis, Missouri 63110, USA.
Mol Biol Cell. 1998 Apr;9(4):865-74. doi: 10.1091/mbc.9.4.865.
The carboxyl-terminal domain of thrombospondin-1 enhances the migration and proliferation of smooth muscle cells. Integrin-associated protein (IAP or CD47) is a receptor for the thrombospondin-1 carboxyl-terminal cell-binding domain and binds the agonist peptide 4N1K (kRFYVVMWKk) from this domain. 4N1K peptide stimulates chemotaxis of both human and rat aortic smooth muscle cells on gelatin-coated filters. The migration on gelatin is specifically blocked by monoclonal antibodies against IAP and a beta1 integrin, rather than alphav beta3 as found previously for 4N1K-stimulated chemotaxis of endothelial cells on gelatin. Both human and rat smooth muscle cells displayed a weak migratory response to soluble type I collagen; however, the presence of 4N1K peptide or intact thrombospondin-1 provoked a synergistic chemotactic response that was partially blocked by antibodies to alpha2 and beta1 integrin subunits and to IAP. A combination of antialpha2 and IAP monoclonal antibodies completely blocked chemotaxis. RGD peptide and antialphav beta3 mAb were without effect. 4N1K and thrombospondin-1 did not augment the chemotactic response of smooth muscle cells to fibronectin, vitronectin, or collagenase-digested type I collagen. Complex formation between alpha2 beta1 and IAP was detected by the coimmunoprecipitation of both alpha2 and beta1 integrin subunits with IAP. These data suggest that IAP can associate with alpha2 beta1 integrin and modulate its function.
血小板反应蛋白-1的羧基末端结构域可增强平滑肌细胞的迁移和增殖。整合素相关蛋白（IAP或CD47）是血小板反应蛋白-1羧基末端细胞结合结构域的受体，可结合该结构域的激动剂肽4N1K（kRFYVVMWKk）。4N1K肽可刺激人及大鼠主动脉平滑肌细胞在明胶包被滤膜上的趋化作用。明胶上的迁移可被抗IAP和β1整合素的单克隆抗体特异性阻断，而非如先前发现的4N1K刺激内皮细胞在明胶上趋化作用时的αvβ3。人和大鼠平滑肌细胞对可溶性I型胶原均表现出较弱的迁移反应；然而，4N1K肽或完整的血小板反应蛋白-1的存在引发了协同趋化反应，该反应被抗α2和β1整合素亚基以及抗IAP的抗体部分阻断。抗α2和IAP单克隆抗体的组合完全阻断了趋化作用。RGD肽和抗αvβ3单克隆抗体无效。4N1K和血小板反应蛋白-1并未增强平滑肌细胞对纤连蛋白、玻连蛋白或胶原酶消化的I型胶原的趋化反应。通过IAP与α2和β1整合素亚基的共免疫沉淀检测到α2β1与IAP之间形成复合物。这些数据表明IAP可与α2β1整合素结合并调节其功能。
