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PMID:23148218
| Citation |
Doppler, H, Bastea, LI, Eiseler, T and Storz, P' (2012) Neuregulin mediates F-actin-driven cell migration through inhibition of Protein Kinase D1 via Rac1. J. Biol. Chem. ' |
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| Abstract |
Neuregulin (NRG, Heregulin) is overexpressed in approximately 30% of breast cancers and mediates various processes involved in tumor progression including tumor cell migration and invasion. Here we show that NRG mediates its effects on tumor cell migration via Protein Kinase D1 (PKD1). Downstream of RhoA, PKD1 can prevent directed cell migration through phosphorylation of its substrate Slingshot 1L (SSH1L). NRG exerts its inhibitory effects on PKD1 through Rac1/NADPH oxidase, leading to decreased PKD1 activation loop phosphorylation and decreased activity towards SSH1L. Consequence of PKD1 inhibition by NRG is decreased binding of 14-3-3 to SSH1L, localization of SSH1L to F-actin at the leading edge and increased cofilin activity, resulting in increased reorganization of the actin cytoskeleton and cell motility. Our data provide a mechanism of how the Rho GTPase Rac1 crosstalks with PKD1 signaling pathways to facilitate directed cell migration. |
| Links |
PubMed Online version:10.1074/jbc.M112.397448 |
| Keywords |
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Significance
Annotations
| Gene product | Qualifier | GO Term | Evidence Code | with/from | Aspect | Extension | Notes | Status |
|---|---|---|---|---|---|---|---|---|
| GO:0019887: protein kinase regulator activity |
ECO:0000314: |
F |
Figure 2 shows that depletion of PKD1 from cells increased their ability to migrate. Data suggests that inhibition of endogenous basal PKD1 activity is a mechanism of how NRG induces cell migration. |
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See also
References
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