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Negative regulation of MAP kinase signaling in Drosophila by Ptp61F/PTP1B

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Abstract

PTP1B is an important negative regulator of insulin and other signaling pathways in mammals. However, the role of PTP1B in the regulation of RAS-MAPK signaling remains open to deliberation, due to conflicting evidence from different experimental systems. The Drosophila orthologue of mammalian PTP1B, PTP61F, has until recently remained largely uncharacterized. To establish the potential role of PTP61F in the regulation of signaling pathways in Drosophila and particularly to help resolve its fundamental function in RAS-MAPK signaling, we generated a new allele of Ptp61F as well as employed both RNA interference and overexpression alleles. Our results validate recent data showing that the activity of insulin and Abl kinase signaling is increased in Ptp61F mutants and RNA interference lines. Importantly, we establish negative regulation of the RAS/MAPK pathway by Ptp61F activity in whole animals. Of particular interest, our results document the modulation of hyperactive MAP kinase activity by Ptp61F alleles, showing that the phosphatase intervenes to directly or indirectly regulate MAP kinase itself.

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Acknowledgments

Drosophila stocks were graciously provided by Norbert Perrimon and Rich Binari, Marc Halfon, the Indiana University Drosophila stock center, the Drosophila Genetic Resource Center, Kyoto Japan, and the Vienna Drosophila RNAi Center. François Brisset, CNRS-ICCMO, Univ. Paris Sud, Orsay, was of invaluable help in preparing the scanning electron micrographs. We also thank Bernadette Wiszniowski for help with Drosophila stocks, and particularly thank Jaesob Kim for help in obtaining the GE29087 P-element insertion in Ptp61F. Funding was provided by the Université de Paris Sud and the CNRS. This work was submitted as partial requirement for completion of a doctoral thesis for S.T-N, who was supported by a fellowship from CoDDIM, Région Ile de France.

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Authors and Affiliations

  1. Université Paris Sud, UMR 8195, Bâtiment 442bis, 91400, Orsay, France

    Stéphane Tchankouo-Nguetcheu, Mario Udinotti, Marjorie Durand, Mohammed Taouis & Leonard Rabinow

  2. Institute of Biological Chemistry, Academia Sinica, 128 Academia Road Sec. 2, Nankang, Taipei, 115, Taiwan

    Tzu-Ching Meng

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  1. Stéphane Tchankouo-Nguetcheu
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  2. Mario Udinotti
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  3. Marjorie Durand
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  4. Tzu-Ching Meng
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  5. Mohammed Taouis
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  6. Leonard Rabinow
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Correspondence to Leonard Rabinow.

Additional information

Communicated by S. Hohmann.

Sequence data from this article have been deposited with the GenBank/EMBL data libraries under accession no. KF695424.

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Tchankouo-Nguetcheu, S., Udinotti, M., Durand, M. et al. Negative regulation of MAP kinase signaling in Drosophila by Ptp61F/PTP1B. Mol Genet Genomics 289, 795–806 (2014). https://doi.org/10.1007/s00438-014-0852-2

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