Caveolin-1 negatively regulates a metalloprotease-dependent epidermal growth factor receptor transactivation by angiotensin II.
Caveolin-1 negatively regulates a metalloprotease-dependent epidermal growth factor receptor transactivation by angiotensin II.
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DOI：
10.1016/j.yjmcc.2010.12.009
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发表时间：
2011-03
影响因子：
5
通讯作者：
Eguchi S
中科院分区：
文献类型：
--
作者：
Takaguri A;Shirai H;Kimura K;Hinoki A;Eguchi K;Carlile-Klusacek M;Yang B;Rizzo V;Eguchi S
金属蛋白酶，ADAM 17，介导表皮生长因子受体（EGFR）的成熟配体的产生。这是血管紧张素II（AngII）诱导EGFR反式激活导致血管平滑肌细胞（VSMC）肥大和迁移的关键信号步骤。然而，ADAM 17活性的调节机制在很大程度上仍不清楚。在这里，我们假设，小窝蛋白-1（Cav 1），一个小窝，膜微区的主要结构蛋白，参与了ADAM 17的调节。在培养的VSMCs中，感染腺病毒编码Cav 1显着抑制AngII诱导的EGFR配体脱落，EGFR反式激活，ERK激活，肥大和迁移，但不胞内Ca 2+升高。甲基-β-环糊精和菲律宾，试剂，破坏筏结构，都刺激表皮生长因子受体配体脱落和表皮生长因子受体反式激活VSMCs。此外，非去污剂蔗糖梯度膜分离显示，ADAM 17 cofractiated与Cav 1在脂筏。这些结果表明，脂筏，也许小窝提供了一个负调控环境EGFR的反式激活与血管重构诱导的AngII。这些新的发现可能为增强的肾素血管紧张素系统靶向心血管疾病提供重要信息。
A metalloprotease, ADAM17, mediates the generation of mature ligands for the epidermal growth factor receptor (EGFR). This is the key signaling step by which angiotensin II (AngII) induces EGFR transactivation leading to hypertrophy and migration of vascular smooth muscle cells (VSMCs). However, the regulatory mechanism of ADAM17 activity remains largely unclear. Here we hypothesized that caveolin-1 (Cav1), the major structural protein of a caveolae, a membrane microdomain, is involved in the regulation of ADAM17. In cultured VSMCs, infection of adenovirus encoding Cav1 markedly inhibited AngII-induced EGFR ligand shedding, EGFR transactivation, ERK activation, hypertrophy and migration, but not intracellular Ca2+ elevation. Methyl-β-cyclodextrin and filipin, reagents that disrupt raft structure, both stimulated an EGFR ligand shedding and EGFR transactivation in VSMCs. In addition, non-detergent sucrose gradient membrane fractionations revealed that ADAM17 cofractionated with Cav1 in lipid rafts. These results suggest that lipid rafts and perhaps caveolae provide a negative regulatory environment for EGFR transactivation linked to vascular remodeling induced by AngII. These novel findings may provide important information to target cardiovascular diseases under the enhanced renin angiotensin system.
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影响因子：
8.3
作者：
Nakashima, Hidekatsu;Frank, Gerald D.;Eguchi, Satoru
通讯作者：
Eguchi, Satoru
影响因子：
4.8
作者：
Eguchi, S;Iwasaki, H;Inagami, T
通讯作者：
Inagami, T
影响因子：
3.6
作者：
Olivares-Reyes, JA;Shah, BH;Catt, KJ
通讯作者：
Catt, KJ
DOI：
10.1016/j.bbrc.2008.02.134
发表时间：
2008-05-09
影响因子：
3.1
作者：
Ingueneau, Cecile;Huynh-Do, Uyen;Vindis, Cecile
通讯作者：
Vindis, Cecile
DOI：
10.1152/ajpheart.01161.2005
发表时间：
2006-06-01
影响因子：
4.8
作者：
Hassan, Ghada S.;Williams, Terence M.;Lisanti, Michael P.
通讯作者：
Lisanti, Michael P.