Department of Life Sciences, Center for Cell Signaling and Drug Discovery Research, Ewha Womans University, Seoul, Korea.
BMB Rep. 2010 May;43(5):305-10. doi: 10.5483/bmbrep.2010.43.5.305.
Syndecans, cell surface heparansulfate proteoglycans, have been proposed to act as cell surface receptors and/or coreceptors to play critical roles in multiple cellular functions. However, recent reports suggest that the function of syndecans can be further extended through shedding, a cleavage of extracellular domain. Shedding constitutes an additional level for controlling the function of syndecans, providing a means to attenuate and/or regulate amplitude and duration of syndecan signals by modulating the activity of syndecans as cell surface receptors. Whether these remaining cleavage products are still capable of functioning as cell surface receptors to efficiently transduce signals inside of cells is not clear. However, shedding transforms cell surface receptor syndecans into soluble forms, which, like growth factors, may act as novel ligands to induce cellular responses by association with other cell surface receptors. It is becoming interestingly evident that shed syndecans also contribute significantly to syndecan functions in cancer biology. This review presents current knowledge about syndecan shedding and its functional significance, particularly in the context of cancer.
连接蛋白是细胞表面硫酸乙酰肝素蛋白聚糖，据推测可以作为细胞表面受体和/或共受体，在多种细胞功能中发挥关键作用。然而，最近的报告表明，连接蛋白的功能可以通过脱落进一步扩展，即细胞外结构域的裂解。脱落构成了控制连接蛋白功能的附加水平，提供了一种通过调节连接蛋白作为细胞表面受体的活性来减弱和/或调节连接蛋白信号幅度和持续时间的手段。这些剩余的裂解产物是否仍然能够作为细胞表面受体有效地将信号转导到细胞内部尚不清楚。然而，脱落将细胞表面受体连接蛋白转化为可溶性形式，这些形式类似于生长因子，可能通过与其他细胞表面受体结合来作为新型配体诱导细胞反应。有趣的是，脱落的连接蛋白也显著促进了癌症生物学中的连接蛋白功能。本文综述了目前关于连接蛋白脱落及其功能意义的知识，特别是在癌症中的意义。
