Rho-ROCK-LIMK-cofilin pathway regulates shear stress activation of sterol regulatory element binding proteins.

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 Res

journal_title

Circulation research

authors

Lin T,Zeng L,Liu Y,DeFea K,Schwartz MA,Chien S,Shyy JY

doi

10.1161/01.RES.0000078780.65824.8B

subject

Has Abstract

pub_date

2003-06-27 00:00:00

pages

1296-304

issue

12

eissn

0009-7330

issn

1524-4571

pii

01.RES.0000078780.65824.8B

journal_volume

92

pub_type

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