A POTENT INHIBITOR OF ENDOTHELIAL-CELL PROLIFERATION IS GENERATED BY PROTEOLYTIC CLEAVAGE OF THE CHEMOKINE PLATELET FACTOR-4
A POTENT INHIBITOR OF ENDOTHELIAL-CELL PROLIFERATION IS GENERATED BY PROTEOLYTIC CLEAVAGE OF THE CHEMOKINE PLATELET FACTOR-4
复制标题
DOI：
10.1073/pnas.92.17.7799
复制
发表时间：
1995-08-15
影响因子：
11.1
通讯作者：
SINGH, JP
中科院分区：
文献类型：
--
作者：
GUPTA, SK;HASSEL, T;SINGH, JP
血小板因子4(PF-4)是在损伤反应和炎症反应中起重要作用的低分子蛋白家族中的一个原型，我们从活化的人白细胞培养上清液中分离出一种能够有效抑制内皮细胞增殖的PF-4。PF-4衍生物是通过Thr-16和Ser-17之间的肽键断裂而产生的，Ser-17位于高度保守和结构重要的CXC基序的下游。这种独特的切割导致PF-4分子中一个结构上重要的大环的丢失，并产生一个带有碱性残基的N末端，该N末端可能与G蛋白偶联趋化因子受体的酸性胞外区相互作用。N-末端处理的PF-4对内皮细胞的生长抑制活性是PF-4的30-50倍，由于内皮细胞生长抑制是切割后的PF-4唯一已知的细胞活性，我们将这种趋化因子命名为内皮细胞生长抑制因子。在组织损伤、炎症和肿瘤形成过程中，PF-4的N端处理可能是调节内皮细胞上PF-4活性的重要机制。
Platelet factor 4 (PF-4) is an archetype of the ''chemokine'' family of low molecular weight proteins that play an important role in injury responses and inflammation, From activated human leukocyte culture supernatants, we have isolated a form of PF-4 that acts as a potent inhibitor of endothelial cell proliferation. The PF-4 derivative is generated by peptide bond cleavage between Thr-16 and Ser-17, a site located downstream from the highly conserved and structurally important CXC motif. The unique cleavage leads to a loss of one of the structurally important large loops in the PF-4 molecule and generation of an N terminus with basic residues that have the potential to interact with the acidic extracellular domain of the G-protein-coupled chemokine receptor. The N-terminal processed PF-4 exhibited a 30- to 50-fold greater growth inhibitory activity on endothelial cells than PF-4, Since endothelial cell growth inhibition is the only known cellular activity of the cleaved PF 4, we have designated this chemokine endothelial cell growth inhibitor. The N-terminal processing of PF-4 may represent an important mechanism for modulating PF 4 activity on endothelial cells during tissue injury, inflammation, and neoplasia.