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  The tyrosine phsophatase Shp2 (PTPN11) directs Neuregulin-1/ErbB signaling throughout Schwann cell development.

Grossmann, K. S., Wende, H., Paul, F. E., Cheret, C., Garratt, A. N., Zurborg, S., et al. (2009). The tyrosine phsophatase Shp2 (PTPN11) directs Neuregulin-1/ErbB signaling throughout Schwann cell development. Proceedings of the National Academy of Sciences of the United States of America, 106(39), 16704-16709. doi:10.1073/pnas.0904336106.

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Item Permalink: http://hdl.handle.net/11858/00-001M-0000-0012-09BC-8 Version Permalink: http://hdl.handle.net/11858/00-001M-0000-002B-C526-E
Genre: Journal Article

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 Creators:
Grossmann, Katja S.1, 2, Author
Wende, Hagen1, Author
Paul, Florian E.3, Author
Cheret, Cyril1, Author
Garratt, Alistair N.1, Author
Zurborg, Sandra4, Author              
Feinberg, Konstantin5, Author
Besser, Daniel2, Author
Schultz, Herbert3, Author
Peles, Elior5, Author
Selbach, Matthias3, Author
Birchmeier, Walter2, Author
Birchmeier, Carmen1, Author
Affiliations:
1Neuroscience Department, Max-Delbrück-Centrum for Molecular Medicine, Robert-Rössle-Strasse 10, 13125 Berlin, Germany, ou_persistent22              
2Department of Cancer Research, Max-Delbrück-Centrum for Molecular Medicine, Robert-Rössle-Strasse 10, 13125 Berlin, Germany, ou_persistent22              
3Department of Cardiovascular Research, Max-Delbrück-Centrum for Molecular Medicine, Robert-Rössle-Strasse 10, 13125 Berlin, Germany, ou_persistent22              
4EMBL Monterotondo, Adriano Buzzati-Traverso Campus, Via Ramarini 32, 00016 Monterotondo, Italy, ou_persistent22              
5Weizmann Institute of Science, PO Box PO Box 26, Rehovot 76100, Israel, ou_persistent22              

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 Abstract: The nonreceptor tyrosine phosphatase Shp2 (PTPN11) has been implicated in tyrosine kinase, cytokine, and integrin receptor signaling. We show here that conditional mutation of Shp2 in neural crest cells and in myelinating Schwann cells resulted in deficits in glial development that are remarkably similar to those observed in mice mutant for Neuregulin-1 (Nrg1) or the Nrg1 receptors, ErbB2 and ErbB3. In cultured Shp2 mutant Schwann cells, Nrg1-evoked cellular responses like proliferation and migration were virtually abolished, and Nrg1-dependent intracellular signaling was altered. Pharmacological inhibition of Src family kinases mimicked all cellular and biochemical effects of the Shp2 mutation, implicating Src as a primary Shp2 target during Nrg1 signaling. Together, our genetic and biochemical analyses demonstrate that Shp2 is an essential component in the transduction of Nrg1/ErbB signals.

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 Dates: 2009-09-29
 Publication Status: Published in print
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 Identifiers: DOI: 10.1073/pnas.0904336106
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Title: Proceedings of the National Academy of Sciences of the United States of America
  Other : Proc. Natl. Acad. Sci. U. S. A.
Source Genre: Journal
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Pages: - Volume / Issue: 106 (39) Sequence Number: - Start / End Page: 16704 - 16709 Identifier: ISSN: 0027-8424
CoNE: https://pure.mpg.de/cone/journals/resource/954925427230