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A pathway of neuregulin-induced activation of cofilin-phosphatase Slingshot and cofilin in lamellipodia
- Source :
- The Journal of Cell Biology
- Publication Year :
- 2004
- Publisher :
- The Rockefeller University Press, 2004.
-
Abstract
- Cofilin mediates lamellipodium extension and polarized cell migration by stimulating actin filament dynamics at the leading edge of migrating cells. Cofilin is inactivated by phosphorylation at Ser-3 and reactivated by cofilin-phosphatase Slingshot-1L (SSH1L). Little is known of signaling mechanisms of cofilin activation and how this activation is spatially regulated. Here, we show that cofilin-phosphatase activity of SSH1L increases approximately 10-fold by association with actin filaments, which indicates that actin assembly at the leading edge per se triggers local activation of SSH1L and thereby stimulates cofilin-mediated actin turnover in lamellipodia. We also provide evidence that 14-3-3 proteins inhibit SSH1L activity, dependent on the phosphorylation of Ser-937 and Ser-978 of SSH1L. Stimulation of cells with neuregulin-1beta induced Ser-978 dephosphorylation, translocation of SSH1L onto F-actin-rich lamellipodia, and cofilin dephosphorylation. These findings suggest that SSH1L is locally activated by translocation to and association with F-actin in lamellipodia in response to neuregulin-1beta and 14-3-3 proteins negatively regulate SSH1L activity by sequestering it in the cytoplasm.
- Subjects :
- Cytoplasm
Tyrosine 3-Monooxygenase
Neuregulin-1
macromolecular substances
Biology
Microfilament
environment and public health
Lim kinase
Dephosphorylation
LIM-kinase
cell polarity
14-3-3
actin filaments
MCF-7
Cell Movement
Report
Cell Line, Tumor
Chlorocebus aethiops
Phosphoprotein Phosphatases
Animals
Humans
Pseudopodia
Phosphorylation
Actin
Microfilament Proteins
Cell Biology
Cofilin
Actin cytoskeleton
Cell biology
Up-Regulation
Actin Cytoskeleton
Protein Transport
14-3-3 Proteins
Actin Depolymerizing Factors
COS Cells
Lamellipodium
Signal Transduction
Subjects
Details
- Language :
- English
- ISSN :
- 15408140 and 00219525
- Volume :
- 165
- Issue :
- 4
- Database :
- OpenAIRE
- Journal :
- The Journal of Cell Biology
- Accession number :
- edsair.doi.dedup.....0f8824f97c87fdd855dfb3a7fb7569ca