Abstract:
:Previous studies have shown that integrin activation and fluid shear stress can modulate the activity of sterol regulatory element binding proteins (SREBPs) in vascular endothelial cells. We investigated the role of small GTPase Rho-mediated signal transduction pathway in this mode of SREBP activation. Fluid shear stress activates the Rho downstream effectors ROCK, LIM kinase (LIMK), and cofilin. The various negative mutants of RhoA, ROCK, LIMK, and cofilin can block the shear stress activation of SREBPs. The shear stress-activated SREBP depends on S2P proteases but not caspase-3. Mechanistically, the endoplasmic reticulum-to-Golgi transport of SREBP cleavage-activating protein requires the actin-based cytoskeleton and is enhanced by the Rho-ROCK-LIMK-cofilin pathway. By enhancing the SREBP-mediated cholesterol metabolism, this unique mechanism may contribute to endothelial cell functions under flow.
journal_name
Circ Resjournal_title
Circulation researchauthors
Lin T,Zeng L,Liu Y,DeFea K,Schwartz MA,Chien S,Shyy JYdoi
10.1161/01.RES.0000078780.65824.8Bsubject
Has Abstractpub_date
2003-06-27 00:00:00pages
1296-304issue
12eissn
0009-7330issn
1524-4571pii
01.RES.0000078780.65824.8Bjournal_volume
92pub_type
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