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

Research output: Contribution to journalArticle

21 Citations (Scopus)

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.

Original languageEnglish (US)
Article numbere30447
JournalPloS one
Volume7
Issue number1
DOIs
StatePublished - Jan 18 2012

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src-Family Kinases
mitogen-activated protein kinase
Phosphoric Monoester Hydrolases
phosphotransferases (kinases)
Phosphotransferases
breast neoplasms
neoplasms
Breast Neoplasms
Tumors
Neoplasms
mutation
Mutation
oncogenes
Oncogenes
Immunoprecipitation
phosphorylation
Phosphorylation
Ligands
Phenotype
phenotype

ASJC Scopus subject areas

  • Biochemistry, Genetics and Molecular Biology(all)
  • Agricultural and Biological Sciences(all)
  • General

Cite this

ErbB2, EphrinB1, Src kinase and PTPN13 signaling complex regulates MAP kinase signaling in human cancers. / Vermeer, Paola D.; Bell, Megan; Lee, Kimberly; Vermeer, Daniel W.; Wieking, Byrant G.; Bilal, Erhan; Bhanot, Gyan; Drapkin, Ronny I.; Ganesan, Shridar; Klingelhutz, Aloysius J.; Hendriks, Wiljan J.; Lee, John H.

In: PloS one, Vol. 7, No. 1, e30447, 18.01.2012.

Research output: Contribution to journalArticle

Vermeer, PD, Bell, M, Lee, K, Vermeer, DW, Wieking, BG, Bilal, E, Bhanot, G, Drapkin, RI, Ganesan, S, Klingelhutz, AJ, Hendriks, WJ & Lee, JH 2012, 'ErbB2, EphrinB1, Src kinase and PTPN13 signaling complex regulates MAP kinase signaling in human cancers', PloS one, vol. 7, no. 1, e30447. https://doi.org/10.1371/journal.pone.0030447
Vermeer, Paola D. ; Bell, Megan ; Lee, Kimberly ; Vermeer, Daniel W. ; Wieking, Byrant G. ; Bilal, Erhan ; Bhanot, Gyan ; Drapkin, Ronny I. ; Ganesan, Shridar ; Klingelhutz, Aloysius J. ; Hendriks, Wiljan J. ; Lee, John H. / ErbB2, EphrinB1, Src kinase and PTPN13 signaling complex regulates MAP kinase signaling in human cancers. In: PloS one. 2012 ; Vol. 7, No. 1.
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