NDLI: Neuregulin mediates F-actin-driven cell migration through inhibition of protein kinase D1 via Rac1 protein.

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Neuregulin mediates F-actin-driven cell migration through inhibition of protein kinase D1 via Rac1 protein.

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Neuregulin mediates F-actin-driven cell migration through inhibition of protein kinase D1 via Rac1 protein.

Content Provider	World Health Organization (WHO)-Global Index Medicus
Author	Bastea, Ligia I. Eiseler, Tim Storz, Peter Döppler, Heike
Description	Author Affiliation: Döppler H ( Department of Cancer Biology, Mayo Clinic Comprehensive Cancer Center, Mayo Clinic, Jacksonville, Florida 32224, USA.)
Abstract	Neuregulin (NRG; heregulin) is overexpressed in â ¼30% 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 PKD1. Downstream of RhoA, PKD1 can prevent directed cell migration through phosphorylation of its substrate SSH1L. NRG exerts its inhibitory effects on PKD1 through Rac1/NADPH oxidase, leading to decreased PKD1 activation loop phosphorylation and decreased activity toward SSH1L. The 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 through which the Rho GTPase Rac1 cross-talks with PKD1 signaling pathways to facilitate directed cell migration.
ISSN	00219258
e-ISSN	1083351X
Journal	Journal of Biological Chemistry
Issue Number	1
Volume Number	288
Language	English
Publisher	American Society for Biochemistry and Molecular Biology (United States)
Publisher Date	2013-01-04
Publisher Place	United States
Access Restriction	Open
Subject Keyword	Actins Metabolism Neuregulin-1 Protein Kinase C Rac1 GTP-Binding Protein Animals Breast Neoplasms Cell Movement Chemotaxis Disease Progression Mice Microscopy, Fluorescence Neoplasm Invasiveness Neoplasm Metastasis RNA, Small Interfering Signal Transduction Wound Healing Research Support, N.I.H., Extramural Research Support, Non-U.S. Gov't Biochemistry Molecular Biology
Content Type	Text
Resource Type	Article
Subject	Cell Biology Biochemistry Molecular Biology

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