Shedding light on proteolytic cleavage of CD44: the responsible sheddase and functional significance of shedding.
Shedding light on proteolytic cleavage of CD44: the responsible sheddase and functional significance of shedding.
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DOI：
10.1038/jid.2009.13
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发表时间：
2009-06
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CD 44是透明质酸的主要细胞表面受体，其涉及细胞-细胞和细胞-基质粘附、细胞迁移和信号传导。研究表明，CD 44依赖性迁移需要CD 44从细胞表面脱落，基质金属蛋白酶介导的裂解可能提供了一种潜在的机制。然而，可能参与CD 44脱落的蛋白酶的全谱尚未确定。Anderegg等人在这篇文章中证明，在人黑素瘤细胞中，ADAM 10（而非ADAM 17或MMP 14）介导CD 44的组成性脱落，并且敲低ADAM 10可阻断CD 44可溶性蛋白水解裂解产物的抗增殖活性。
CD44 is the major cell-surface receptor for hyaluronan, which is implicated in cell–cell and cell–matrix adhesion, cell migration, and signaling. Studies have shown that CD44-dependent migration requires CD44 to be shed from the cell surface and that matrix metalloproteinase–mediated cleavage may provide an underlying mechanism. However, the full spectrum of proteases that may participate in CD44 shedding has yet to be defined. In this issue, Anderegg et al. demonstrate that ADAM10, but not ADAM17 or MMP14, mediates constitutive shedding of CD44 in human melanoma cells and that knockdown of ADAM10 blocks the antiproliferative activity of the soluble proteolytic cleavage product of CD44.