This model is described in the article:
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.
This model is hosted on BioModels Database and identified by: BIOMD0000000557.
To cite BioModels Database, please use: BioModels Database: An enhanced, curated and annotated resource for published quantitative kinetic models.
To the extent possible under law, all copyright and related or neighbouring rights to this encoded model have been dedicated to the public domain worldwide. Please refer to CC0 Public Domain Dedication for more information.
-
Pseudophosphatase STYX modulates cell-fate decisions and cell migration by spatiotemporal regulation of ERK1/2.
- Veronika Reiterer, Dirk Fey, Walter Kolch, Boris N Kholodenko, Hesso Farhan
- Proceedings of the National Academy of Sciences of the United States of America , 7/ 2013 , Volume 110 , Issue 31 , pages: E2934-43 , PubMed ID: 23847209
- Biotechnology Institute Thurgau, University of Konstanz, Kreuzlingen, Switzerland.
- 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.
Submitter of this revision: Lucian Smith
Curator: Lucian Smith
Modeller: Dirk Fey
Metadata information
isDescribedBy (1 statement)
hasTaxon (1 statement)
isVersionOf (1 statement)
occursIn (1 statement)
hasProperty (1 statement)
Connected external resources
SBGN view in Newt Editor
