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PMID: 15210733 Published · ppublish English Journal Article Research Support, Non-U.S. Gov't

Plexin-B1/RhoGEF-mediated RhoA activation involves the receptor tyrosine kinase ErbB-2.

The Journal of cell biology ·Vol. 165 ·No. 6 ·2004-06-21 ·Pages 869-80

Swiercz JM, Kuner R, Offermanns S

Abstract

Plexins are widely expressed transmembrane proteins that mediate the effects of semaphorins. The molecular mechanisms of plexin-mediated signal transduction are still rather unclear. Plexin-B1 has recently been shown to mediate activation of RhoA through a stable interaction with the Rho guanine nucleotide exchange factors PDZ-RhoGEF and LARG. However, it is unclear how the activity of plexin-B1 and its downstream effectors is regulated by its ligand Sema4D. Here, we show that plexin-B family members stably associate with the receptor tyrosine kinase ErbB-2. Binding of Sema4D to plexin-B1 stimulates the intrinsic tyrosine kinase activity of ErbB-2, resulting in the phosphorylation of both plexin-B1 and ErbB-2. A dominant-negative form of ErbB-2 blocks Sema4D-induced RhoA activation as well as axonal growth cone collapse in primary hippocampal neurons. Our data indicate that ErbB-2 is an important component of the plexin-B receptor system and that ErbB-2-mediated phosphorylation of plexin-B1 is critically involved in Sema4D-induced RhoA activation, which underlies cellular phenomena downstream of plexin-B1, including axonal growth cone collapse.

MeSH Terms
Alkaline Phosphatase/metabolism Animals COS Cells Cell Division Chlorocebus aethiops Chromatography, Affinity Enzyme Activation Guanine Nucleotide Exchange Factors/metabolism HeLa Cells Humans Nerve Tissue Proteins/metabolism Phosphorylation Receptor, ErbB-2/metabolism Receptors, Cell Surface/metabolism Rho Guanine Nucleotide Exchange Factors rhoA GTP-Binding Protein/metabolism
Chemicals
Guanine Nucleotide Exchange Factors Nerve Tissue Proteins PLXNB1 protein, human Receptors, Cell Surface Rho Guanine Nucleotide Exchange Factors Receptor, ErbB-2 Alkaline Phosphatase rhoA GTP-Binding Protein
Authors & Affiliations
3 authors, click to expand affiliations / ORCID
Swiercz Jakub M
Institute of Pharmacology, University of Heidelberg, Im Neuenheimer Feld 366, 69120 Heidelberg, Germany.
Kuner Rohini
Offermanns Stefan
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Article Info
Journal
The Journal of cell biology
Abbr.
J Cell Biol
ISSN
0021-9525
DOI
10.1083/jcb.200312094
Published
2004-06-21
Pages
869-80
Language
English
Region
United States
NLM ID
0375356
PMCID
PMC2172401
Subset
IM
External Links
PubMed source DOI: 10.1083/jcb.200312094 PMC Full Text View journal details
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