期刊
MOLECULAR BIOLOGY OF THE CELL
卷 20, 期 11, 页码 2650-2660出版社
AMER SOC CELL BIOLOGY
DOI: 10.1091/mbc.E09-02-0131
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资金
- National Institutes of Health [HL48008, GM44428]
- American Heart Association, Western affiliate
Cellular stimuli generate reactive oxygen species (ROS) via the local action of NADPH oxidases (Nox) to modulate cytoskeletal organization and cell migration through unknown mechanisms. Cofilin is a major regulator of cellular actin dynamics whose activity is controlled by phosphorylation/dephosphorylation at Ser3. Here we show that Slingshot-1L (SSH-1L), a selective cofilin regulatory phosphatase, is involved in H2O2-induced cofilin dephosphorylation and activation. SSH-1L is activated by its release from a regulatory complex with 14-3-3 zeta protein through the redox-mediated oxidation of 14-3-3 zeta by H2O2. The ROS-dependent activation of the SSH-1L-cofilin pathway stimulates the SSH-1L dependent formation of cofilin-actin rods in cofilin-GFP-expressing HeLa cells. Similarly, the formation of endogenous ROS stimulated by angiotensin II (AngII) also activates the SSH-1L-cofilin pathway via oxidation of 14-3-3 zeta to increase AngII-induced membrane ruffling and cell motility. These results suggest that the formation of ROS by NADPH oxidases engages a SSH-1L-cofilin pathway to regulate cytoskeletal organization and cell migration.
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