Maurer Anne-Marie, Zhou Bin, Han Zhong Chao
Marmara University School of Medicine, Istanbul, Turkey.
Growth Factors. 2006 Dec;24(4):242-52. doi: 10.1080/08977190600988225.
Platelet factor 4 (PF4) has been recognized as a physiological inhibitor of megakaryocytopoiesis and angiogenesis for two decades. Structure-function studies have shown that the DLQ determinant in position 54-56 is necessary for megakaryocytic inhibition whereas mutations of these residues into ELR sequence and more importantly, into DLR sequence, induce a stronger inhibitory activity of peptide p47-70 on angiogenesis. The alpha-helix region of peptides may participate in the fixation of the effector to its cellular receptor and the other important structural domains would activate the receptor. In vivo, PF4 and its related peptides can protect hematopoiesis from chemotherapy by enhancing cell viability and suppress tumor growth through anti-angiogenic pathway. Several PF4 fragments and modified molecules exhibit antiangiogenesis properties and may become an alternative for further therapeutic angiogenesis.
二十年来，血小板因子4（PF4）一直被认为是巨核细胞生成和血管生成的生理抑制剂。结构功能研究表明，54 - 56位的DLQ决定簇是巨核细胞抑制所必需的，而这些残基突变为ELR序列，更重要的是突变为DLR序列，会诱导肽p47 - 70对血管生成产生更强的抑制活性。肽的α - 螺旋区域可能参与效应物与细胞受体的结合，而其他重要的结构域则会激活受体。在体内，PF4及其相关肽可通过提高细胞活力保护造血功能免受化疗影响，并通过抗血管生成途径抑制肿瘤生长。几种PF4片段和修饰分子具有抗血管生成特性，可能成为进一步治疗性血管生成的替代物。
