Pseudophosphatase STYX modulates cell-fate decisions and cell migration by spatiotemporal regulation of ERK1/2

Reiterer, Veronika; Fey, Dirk; Kolch, Walter; Kholodenko, Boris N.; Farhan, Hesso

Pseudophosphatase STYX modulates cell-fate decisions and cell migration by spatiotemporal regulation of ERK1/2

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Date

2013

Authors

Reiterer, Veronika

Fey, Dirk

Kolch, Walter

Kholodenko, Boris N.

Farhan, Hesso

DOI (citable link)

10.1073/pnas.1301985110

Collections

Biologie

Publication type

Journal article

Published in

Proceedings of the National Academy of Sciences of the United States of America : PNAS ; 110 (2013), 31. - pp. E2934-E2943. - ISSN 0027-8424. - eISSN 1091-6490

Abstract

Serine/threonine/tyrosine-interacting protein (STYX) is a catalytically inactive member of the dual-specificity phosphatases (DUSPs) family. Whereas the role of DUSPs in cellular signaling is well explored, the function of STYX is still unknown. Here, we identify STYX as a spatial regulator of ERK signaling. We used predictive-model simulation to test several hypotheses for possible modes of STYX action. We show that STYX localizes to the nucleus, competes with nuclear DUSP4 for binding to ERK, and acts as a nuclear anchor that regulates ERK nuclear export. Depletion of STYX increases ERK activity in both cytosol and nucleus. Importantly, depletion of STYX causes an ERK-dependent fragmentation of the Golgi apparatus and inhibits Golgi polarization and directional cell migration. Finally, we show that overexpression of STYX reduces ERK1/2 activation, thereby blocking PC12 cell differentiation. Overall, our results identify STYX as an important regulator of ERK1/2 signaling critical for cell migration and PC12 cell differentiation.

Subject (DDC)

570 Biosciences, Biology

Cite This

ISO 690

REITERER, Veronika, Dirk FEY, Walter KOLCH, Boris N. KHOLODENKO, Hesso FARHAN, 2013. Pseudophosphatase STYX modulates cell-fate decisions and cell migration by spatiotemporal regulation of ERK1/2. In: Proceedings of the National Academy of Sciences of the United States of America : PNAS. 110(31), pp. E2934-E2943. ISSN 0027-8424. eISSN 1091-6490. Available under: doi: 10.1073/pnas.1301985110

BibTex

@article{Reiterer2013Pseud-29406,
  year={2013},
  doi={10.1073/pnas.1301985110},
  title={Pseudophosphatase STYX modulates cell-fate decisions and cell migration by spatiotemporal regulation of ERK1/2},
  number={31},
  volume={110},
  issn={0027-8424},
  journal={Proceedings of the National Academy of Sciences of the United States of America : PNAS},
  pages={E2934--E2943},
  author={Reiterer, Veronika and Fey, Dirk and Kolch, Walter and Kholodenko, Boris N. and Farhan, Hesso}
}

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Bibliography of Konstanz

Yes