Cell-matrix interaction via CD44 is independently regulated by different metalloproteinases activated in response to extracellular Ca(2+) influx and PKC activation.
Cell-matrix interaction via CD44 is independently regulated by different metalloproteinases activated in response to extracellular Ca(2+) influx and PKC activation.
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DOI：
10.1083/jcb.200310024
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发表时间：
2004-06-21
期刊：
影响因子：
--
通讯作者：
Saya H
中科院分区：
文献类型：
--
作者：
Nagano O;Murakami D;Hartmann D;De Strooper B;Saftig P;Iwatsubo T;Nakajima M;Shinohara M;Saya H
CD44是一种粘附分子，可与透明质酸（HA）相互作用，并在其外膜结构域和膜内结构域发生连续的蛋白水解裂解。胞外Ca2+内流或蛋白激酶c的激活触发胞外结构域切割。在这里，我们发现cd44介导的细胞基质粘附被两个独立的ADAM家族金属蛋白酶ADAM10和ADAM17终止，ADAM10和ADAM17在响应这些刺激时受到不同的调节。Ca2+内流通过调节钙调蛋白和ADAM10之间的联系激活ADAM10，导致CD44外畴切割。ADAM10的缺失强烈抑制Ca2+流入诱导的细胞脱离基质。另一方面，苯酚酯刺激通过激活PKC和小GTPase Rac激活ADAM17，诱导CD44的蛋白水解。此外，ADAM10或ADAM17的缺失显著抑制了依赖cd44的癌细胞对HA的迁移，而对纤维连接蛋白没有作用。CD44切割的两条独立信号通路的时空调控在细胞-基质相互作用和细胞迁移中起着至关重要的作用。
CD44 is an adhesion molecule that interacts with hyaluronic acid (HA) and undergoes sequential proteolytic cleavages in its ectodomain and intramembranous domain. The ectodomain cleavage is triggered by extracellular Ca2+ influx or the activation of protein kinase C. Here we show that CD44-mediated cell–matrix adhesion is terminated by two independent ADAM family metalloproteinases, ADAM10 and ADAM17, differentially regulated in response to those stimuli. Ca2+ influx activates ADAM10 by regulating the association between calmodulin and ADAM10, leading to CD44 ectodomain cleavage. Depletion of ADAM10 strongly inhibits the Ca2+ influx-induced cell detachment from matrix. On the other hand, phorbol ester stimulation activates ADAM17 through the activation of PKC and small GTPase Rac, inducing proteolysis of CD44. Furthermore, depletion of ADAM10 or ADAM17 markedly suppressed CD44-dependent cancer cell migration on HA, but not on fibronectin. The spatio-temporal regulation of two independent signaling pathways for CD44 cleavage plays a crucial role in cell–matrix interaction and cell migration.
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膜型1基质金属蛋白酶切割CD44并促进细胞迁移。
影响因子：
7.8
作者：
Kajita, M;Itoh, Y;Chiba, T;Mori, H;Okada, A;Kinoh, H;Seiki, M
通讯作者：
Seiki, M
影响因子：
4.8
作者：
Buxbaum, JD;Liu, KN;Black, RA
通讯作者：
Black, RA
影响因子：
4.1
作者：
Díaz-Rodríguez, E;Esparís-Ogando, A;Pandiella, A
通讯作者：
Pandiella, A
影响因子：
3.3
作者：
Díaz-Rodríguez, E;Montero, JC;Pandiella, A
通讯作者：
Pandiella, A
DOI：
10.1073/pnas.96.8.4426
发表时间：
1999-04-13
影响因子：
11.1
作者：
Craske, H;Takeo, T;Tepikin, AV
通讯作者：
Tepikin, AV