Whitelock John M, Melrose James, Iozzo Renato V
Graduate School of Biomedical Engineering, University of New South Wales, Kensington, Australia.
Biochemistry. 2008 Oct 28;47(43):11174-83. doi: 10.1021/bi8013938. Epub 2008 Oct 1.
Perlecan is a ubiquitous pericellular proteoglycan ideally placed to mediate cell signaling events controlling migration, proliferation, and differentiation. Its control of growth factor signaling usually involves interactions with the heparan sulfate chains covalently coupled to the protein core's N-terminus. However, this modular protein core also binds with relatively high affinity to a number of growth factors and surface receptors, thereby stabilizing cell-matrix links. This review will focus on perlecan-growth factor interactions and describe recent advances in our understanding of this highly conserved proteoglycan during development, cancer growth, and angiogenesis. The pro-angiogenic capacities of perlecan that involve proliferative and migratory signals in response to bound growth factors will be explored, as well as the anti-angiogenic signals resulting from interactions between the C-terminal domain known as endorepellin and integrins that control adhesion of cells to the extracellular matrix. These two somewhat diametrically opposed roles will be discussed in light of new data emerging from various fields which converge on perlecan as a key regulator of cell growth and angiogenesis.
基底膜聚糖是一种广泛存在于细胞周围的蛋白聚糖，非常适合介导控制细胞迁移、增殖和分化的细胞信号事件。它对生长因子信号的控制通常涉及与共价连接到蛋白质核心N端的硫酸乙酰肝素链的相互作用。然而，这个模块化的蛋白质核心也以相对较高的亲和力与多种生长因子和表面受体结合，从而稳定细胞与基质的连接。本综述将聚焦于基底膜聚糖与生长因子的相互作用，并描述我们在发育、癌症生长和血管生成过程中对这种高度保守的蛋白聚糖的最新认识进展。将探讨基底膜聚糖的促血管生成能力，其涉及对结合的生长因子产生增殖和迁移信号，以及由称为内源性趋化素的C端结构域与控制细胞与细胞外基质粘附的整合素之间的相互作用产生的抗血管生成信号。鉴于来自各个领域汇聚于基底膜聚糖作为细胞生长和血管生成关键调节因子的新数据，将对这两种几乎截然相反的作用进行讨论。
