Fibrillar collagen inhibits arterial smooth muscle proliferation through regulation of Cdk2 inhibitors

被引：432

作者：

Koyama, H ^{[1
]}

Raines, EW ^{[1
]}

Bornfeldt, KE ^{[1
]}

Roberts, JM ^{[1
]}

Ross, R ^{[1
]}

机构：

[1] FRED HUTCHINSON CANC RES CTR,DEPT BASIC SCI,SEATTLE,WA 98104

来源：

CELL | 1996年 / 87卷 / 06期

关键词：

D O I：

10.1016/S0092-8674(00)81801-2

中图分类号：

Q5 [生物化学]; Q7 [分子生物学];

学科分类号：

071010 ; 081704 ;

摘要：

Arterial smooth muscle cells (SMCs) are arrested in the G1 phase of the cell cycle on polymerized type I collagen fibrils, while monomer collagen supports SMC proliferation. Cyclin E-associated kinase and cyclin-dependent kinase 2 (cdk2) phosphorylation are inhibited on polymerized collagen, and levels of the cdk2 inhibitors p27(Kip1) p21(Cip1/Waf1) increased compared with SMCs on monomer collagen. p27(Kip1) associates with the cyclin E-cdk2-p21(Cip1/Waf1) complex in SMCs on polymerized collagen. Monovalent blocking antibodies to alpha 2 integrins, integrins that mediate adhesion to both forms of collagen, mimic these effects on monomer collagen. Furthermore, polymerized collagen rapidly suppresses p70 S6 kinase, a possible regulator of p27(Kip1). Thus, fibrillar collagen specifically regulates early integrin signaling that may lead to up-regulation of cdk2 inhibitors and inhibition of SMC proliferation.

引用

页码：1069 / 1078

页数：10

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