ErbB2, EphrinB1, Src Kinase and PTPN13 Signaling Complex Regulates MAP Kinase Signaling in Human Cancers

Paola D Vermeer; Megan Bell; Kimberly Lee; Daniel W Vermeer; Byrant G Wieking; Erhan Bilal; Gyan Bhanot; Ronny I Drapkin; Shridar Ganesan; Aloysius J Klingelhutz; Wiljan J Hendriks; John H Lee

doi:10.1371/journal.pone.0030447

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ErbB2, EphrinB1, Src Kinase and PTPN13 Signaling Complex Regulates MAP Kinase Signaling in Human Cancers

Journal article

Open access

Peer reviewed

ErbB2, EphrinB1, Src Kinase and PTPN13 Signaling Complex Regulates MAP Kinase Signaling in Human Cancers

Paola D Vermeer, Megan Bell, Kimberly Lee, Daniel W Vermeer, Byrant G Wieking, Erhan Bilal, Gyan Bhanot, Ronny I Drapkin, Shridar Ganesan, Aloysius J Klingelhutz, …

PloS one, Vol.7(1), pp.e30447-e30447

2012

DOI: 10.1371/journal.pone.0030447

PMCID: PMC3261204

PMID: 22279592

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Abstract

In non-cancerous cells, phosphorylated proteins exist transiently, becoming de-phosphorylated by specific phosphatases that terminate propagation of signaling pathways. In cancers, compromised phosphatase activity and/or expression occur and contribute to tumor phenotype. The non-receptor phosphatase, PTPN13, has recently been dubbed a putative tumor suppressor. It decreased expression in breast cancer correlates with decreased overall survival. Here we show that PTPN13 regulates a new signaling complex in breast cancer consisting of ErbB2, Src, and EphrinB1. To our knowledge, this signaling complex has not been previously described. Co-immunoprecipitation and localization studies demonstrate that EphrinB1, a PTPN13 substrate, interacts with ErbB2. In addition, the oncogenic V660E ErbB2 mutation enhances this interaction, while Src kinase mediates EphrinB1 phosphorylation and subsequent MAP Kinase signaling. Decreased PTPN13 function further enhances signaling. The association of oncogene kinases (ErbB2, Src), a signaling transmembrane ligand (EphrinB1) and a phosphatase tumor suppressor (PTPN13) suggest that EphrinB1 may be a relevant therapeutic target in breast cancers harboring ErbB2-activating mutations and decreased PTPN13 expression.

Medicine

Biology

Details

Title: Subtitle: ErbB2, EphrinB1, Src Kinase and PTPN13 Signaling Complex Regulates MAP Kinase Signaling in Human Cancers
Creators: Paola D Vermeer - Ottawa Hospital Research Institute, Canada
Megan Bell - Ottawa Hospital Research Institute, Canada
Kimberly Lee - Ottawa Hospital Research Institute, Canada
Daniel W Vermeer - Ottawa Hospital Research Institute, Canada
Byrant G Wieking - Ottawa Hospital Research Institute, Canada
Erhan Bilal - Ottawa Hospital Research Institute, Canada
Gyan Bhanot - Ottawa Hospital Research Institute, Canada
Ronny I Drapkin - Ottawa Hospital Research Institute, Canada
Shridar Ganesan - Ottawa Hospital Research Institute, Canada
Aloysius J Klingelhutz - Ottawa Hospital Research Institute, Canada
Wiljan J Hendriks - Ottawa Hospital Research Institute, Canada
John H Lee - Sanford Research
Resource Type: Journal article
Publication Details: PloS one, Vol.7(1), pp.e30447-e30447
DOI: 10.1371/journal.pone.0030447
PMID: 22279592
PMCID: PMC3261204
NLM abbreviation: PLoS One
ISSN: 1932-6203
eISSN: 1932-6203
Publisher: Public Library of Science; San Francisco, USA
Alternative title: ErbB2, EphrinB1, Src and PTPN13 Complex in Cancer
Language: English
Date published: 2012
Academic Unit: Microbiology and Immunology; Radiation Oncology
Record Identifier: 9984001134802771

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