The inositol phosphatase SHIP2 enables sustained ERK activation downstream of FGF receptors by recruiting Src kinases

Bohumil Fafilek; Lukas Balek; Michaela Kunova Bosakova; Miroslav Varecha; Alexandru Nita; Tomas Gregor; Iva Gudernova; Jitka Krenova; Somadri Ghosh; Martin Piskacek; Lucie Jonatova; Nicole H. Cernohorsky; Jennifer T. Zieba; Michal Kostas; Ellen Margrethe Haugsten; Jørgen Wesche; Christophe Erneux; Lukas Trantirek; Deborah Krakow; Pavel Krejci

doi:10.1126/scisignal.aap8608

Research ArticleCell Biology

The inositol phosphatase SHIP2 enables sustained ERK activation downstream of FGF receptors by recruiting Src kinases

Bohumil Fafilek¹,²,*,
Lukas Balek¹,*,
Michaela Kunova Bosakova¹,²,
Miroslav Varecha¹,²,
Alexandru Nita¹,
Tomas Gregor³,
Iva Gudernova¹,
Jitka Krenova¹,
Somadri Ghosh⁴,
Martin Piskacek⁵,
Lucie Jonatova¹,
Nicole H. Cernohorsky¹,
Jennifer T. Zieba ⁶,
Michal Kostas⁷,⁸,
Ellen Margrethe Haugsten⁷,⁸,
Jørgen Wesche⁷,⁸,
Christophe Erneux⁴,
Lukas Trantirek ³,
Deborah Krakow ⁶,⁹,¹⁰, and
Pavel Krejci ¹,²,¹¹,†

¹Department of Biology, Masaryk University, 62500 Brno, Czech Republic.
²International Clinical Research Center, St. Anne’s University Hospital, 65691 Brno, Czech Republic.
³Central European Institute of Technology, Masaryk University, 62500 Brno, Czech Republic.
⁴Institut de Recherche Interdisciplinaire en Biologie Humaine et moléculaire, Université Libre de Bruxelles, 1070 Bruxelles, Belgium.
⁵Department of Pathological Physiology, Faculty of Medicine, Masaryk University, 62500 Brno, Czech Republic.
⁶Department of Orthopedic Surgery, University of California Los Angeles, CA 90095, USA.
⁷Department of Tumor Biology, Institute for Cancer Research, Norwegian Radium Hospital, 0379 Oslo, Norway.
⁸Institute of Clinical Medicine, Faculty of Medicine, University of Oslo, 0379 Oslo, Norway.
⁹Department of Human Genetics, University of California Los Angeles, CA 90095, USA.
¹⁰Department of Obstetrics and Gynecology, David Geffen School of Medicine, University of California Los Angeles, CA 90095, USA.
¹¹Institute of Animal Physiology and Genetics of the Czech Academy of Sciences, 60200 Brno, Czech Republic.

↵†Corresponding author. Email: krejcip{at}med.muni.cz

↵* These authors contributed equally to this work.

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Science Signaling 18 Sep 2018:
Vol. 11, Issue 548, eaap8608
DOI: 10.1126/scisignal.aap8608

Bohumil Fafilek

1Department of Biology, Masaryk University, 62500 Brno, Czech Republic.

2International Clinical Research Center, St. Anne’s University Hospital, 65691 Brno, Czech Republic.

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Lukas Balek

1Department of Biology, Masaryk University, 62500 Brno, Czech Republic.

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Michaela Kunova Bosakova

1Department of Biology, Masaryk University, 62500 Brno, Czech Republic.

2International Clinical Research Center, St. Anne’s University Hospital, 65691 Brno, Czech Republic.

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Miroslav Varecha

1Department of Biology, Masaryk University, 62500 Brno, Czech Republic.

2International Clinical Research Center, St. Anne’s University Hospital, 65691 Brno, Czech Republic.

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Alexandru Nita

1Department of Biology, Masaryk University, 62500 Brno, Czech Republic.

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Tomas Gregor

3Central European Institute of Technology, Masaryk University, 62500 Brno, Czech Republic.

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Iva Gudernova

1Department of Biology, Masaryk University, 62500 Brno, Czech Republic.

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Jitka Krenova

1Department of Biology, Masaryk University, 62500 Brno, Czech Republic.

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Somadri Ghosh

4Institut de Recherche Interdisciplinaire en Biologie Humaine et moléculaire, Université Libre de Bruxelles, 1070 Bruxelles, Belgium.

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Martin Piskacek

5Department of Pathological Physiology, Faculty of Medicine, Masaryk University, 62500 Brno, Czech Republic.

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Lucie Jonatova

1Department of Biology, Masaryk University, 62500 Brno, Czech Republic.

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Nicole H. Cernohorsky

1Department of Biology, Masaryk University, 62500 Brno, Czech Republic.

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Jennifer T. Zieba

6Department of Orthopedic Surgery, University of California Los Angeles, CA 90095, USA.

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Michal Kostas

7Department of Tumor Biology, Institute for Cancer Research, Norwegian Radium Hospital, 0379 Oslo, Norway.

8Institute of Clinical Medicine, Faculty of Medicine, University of Oslo, 0379 Oslo, Norway.

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Ellen Margrethe Haugsten

7Department of Tumor Biology, Institute for Cancer Research, Norwegian Radium Hospital, 0379 Oslo, Norway.

8Institute of Clinical Medicine, Faculty of Medicine, University of Oslo, 0379 Oslo, Norway.

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Jørgen Wesche

7Department of Tumor Biology, Institute for Cancer Research, Norwegian Radium Hospital, 0379 Oslo, Norway.

8Institute of Clinical Medicine, Faculty of Medicine, University of Oslo, 0379 Oslo, Norway.

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Christophe Erneux

4Institut de Recherche Interdisciplinaire en Biologie Humaine et moléculaire, Université Libre de Bruxelles, 1070 Bruxelles, Belgium.

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Lukas Trantirek

3Central European Institute of Technology, Masaryk University, 62500 Brno, Czech Republic.

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Deborah Krakow

6Department of Orthopedic Surgery, University of California Los Angeles, CA 90095, USA.

9Department of Human Genetics, University of California Los Angeles, CA 90095, USA.

10Department of Obstetrics and Gynecology, David Geffen School of Medicine, University of California Los Angeles, CA 90095, USA.

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Pavel Krejci

1Department of Biology, Masaryk University, 62500 Brno, Czech Republic.

2International Clinical Research Center, St. Anne’s University Hospital, 65691 Brno, Czech Republic.

11Institute of Animal Physiology and Genetics of the Czech Academy of Sciences, 60200 Brno, Czech Republic.

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For correspondence: krejcip@med.muni.cz

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vol. 11 no. 548

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https://doi.org/10.1126/scisignal.aap8608

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Received September 4, 2017
Accepted August 29, 2018
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Copyright © 2018 The Authors, some rights reserved; exclusive licensee American Association for the Advancement of Science. No claim to original U.S. Government Works http://www.sciencemag.org/about/science-licenses-journal-article-reuseThis is an article distributed under the terms of the Science Journals Default License.

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The inositol phosphatase SHIP2 enables sustained ERK activation downstream of FGF receptors by recruiting Src kinases

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