CD44 anchors the assembly of matrilysin/MMP-7 with heparin-binding epidermal growth factor precursor and ErbB4 and regulates female reproductive organ remodeling
CD44 anchors the assembly of matrilysin/MMP-7 with heparin-binding epidermal growth factor precursor and ErbB4 and regulates female reproductive organ remodeling
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DOI：
10.1101/gad.925702
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发表时间：
2002-02-01
影响因子：
10.5
通讯作者：
Stamenkovic, I
中科院分区：
文献类型：
--
作者：
Yu, WH;Woessner, JF;Stamenkovic, I
CD 44是一种与细胞粘附和运输以及肿瘤存活和进展有关的兼性蛋白聚糖。我们在这里证明，CD 44硫酸乙酰肝素蛋白聚糖（CD 44 HSPG）招募蛋白水解活性基质金属蛋白酶7（基质溶解素，MMP-7）和肝素结合表皮生长因子前体（前HB-EGF）的肿瘤细胞系，子宫产后和泌乳期乳腺上皮细胞和子宫平滑肌的表面上形成一个复合物。该复合物中的HB-EGF前体由MMP-7加工，所得的成熟HB-EGF接合并激活其受体ErbB 4，导致细胞存活等事件。在CD 44（-/-）小鼠中，产后子宫复旧加速，泌乳维持受损。在这些小鼠的子宫和乳腺上皮中，MMP-7定位改变，pro-HB-EGF加工以及ErbB 4活化降低。我们的观察提供了一种机制，由CD 44 HSPG，MMP 7，HB-EGF和ErbB 4组成的细胞表面复合物的组装和功能，可能在生理组织重塑的调节中发挥重要作用。
CD44 is a facultative proteoglycan implicated in cell adhesion and trafficking, as well as in tumor survival and progression. We demonstrate here that CD44 heparan sulfate proteoglycan (CD44HSPG) recruits proteolytically active matrix metalloproteinase 7 (matrilysin, MMP-7) and heparin-binding epidermal growth factor precursor (pro-HB-EGF) to form a complex on the surface of tumor cell lines, postpartum uterine and lactating mammary gland epithelium, and uterine smooth muscle. The HB-EGF precursor within this complex is processed by MMP-7, and the resulting mature HB-EGF engages and activates its receptor, ErbB4, leading to, among other events, cell survival. In CD44(-/-) mice, postpartum uterine involution is accelerated and maintenance of lactation is impaired. In both uterine and mammary epithelia of these mice, MMP-7 localization is altered and pro-HB-EGF processing as well as ErbB4 activation are decreased. Our observations provide a mechanism for the assembly and function of a cell surface complex composed of CD44HSPG, MMP 7, HB-EGF, and ErbB4 that may play an important role in the regulation of physiological tissue remodeling.