Next Article in Journal
Cell Reprogramming in Tumorigenesis and Its Therapeutic Implications for Breast Cancer
Previous Article in Journal
When CAR Meets Stem Cells
Previous Article in Special Issue
A Ruthenium(II) N-Heterocyclic Carbene (NHC) Complex with Naphthalimide Ligand Triggers Apoptosis in Colorectal Cancer Cells via Activating the ROS-p38 MAPK Pathway
Article Menu
Issue 8 (April-2) cover image

Export Article

Open AccessCommunication

Crosstalk between p38 and Erk 1/2 in Downregulation of FGF1-Induced Signaling

1
Department of Protein Engineering, Faculty of Biotechnology, University of Wroclaw, 50-383 Wroclaw, Poland
2
Department of Tumor Biology, Institute for Cancer Research, Oslo University Hospital, Montebello, 0379 Oslo, Norway
3
Centre for Cancer Cell Reprogramming, Institute of Clinical Medicine, Faculty of Medicine, University of Oslo, Montebello, 0379 Oslo, Norway
4
Department of Molecular Cell Biology, Institute for Cancer Research, Oslo University Hospital, Montebello, 0379 Oslo, Norway
*
Author to whom correspondence should be addressed.
Int. J. Mol. Sci. 2019, 20(8), 1826; https://doi.org/10.3390/ijms20081826
Received: 14 January 2019 / Revised: 25 January 2019 / Accepted: 10 April 2019 / Published: 12 April 2019
  |  
PDF [2956 KB, uploaded 12 April 2019]
  |  

Abstract

Mitogen-activated protein kinases (MAPK): Erk1 and Erk2 are key players in negative-feedback regulation of fibroblast growth factor (FGF) signaling. Upon activation, Erk1 and Erk2 directly phosphorylate FGF receptor 1 (FGFR1) at a specific serine residue in the C-terminal part of the receptor, substantially reducing the tyrosine phosphorylation in the receptor kinase domain and its signaling. Similarly, active Erks can also phosphorylate multiple threonine residues in the docking protein FGF receptor substrate 2 (FRS2), a major mediator of FGFR signaling. Here, we demonstrate that in NIH3T3 mouse fibroblasts and human osteosarcoma U2OS cells stably expressing FGFR1, in addition to Erk1 and Erk2, p38 kinase is able to phosphorylate FRS2. Simultaneous inhibition of Erk1/2 and p38 kinase led to a significant change in the phosphorylation pattern of FRS2 that in turn resulted in prolonged tyrosine phosphorylation of FGFR1 and FRS2 and in sustained signaling, as compared to the selective inhibition of Erks. Furthermore, excessive activation of p38 with anisomycin partially compensated the lack of Erks activity. These experiments reveal a novel crosstalk between p38 and Erk1/2 in downregulation of FGF-induced signaling. View Full-Text
Keywords: FGF-induced signaling; FRS2; phosphorylation; downregulation; p38; MAPK FGF-induced signaling; FRS2; phosphorylation; downregulation; p38; MAPK
Figures

Graphical abstract

This is an open access article distributed under the Creative Commons Attribution License which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly cited (CC BY 4.0).
SciFeed

Share & Cite This Article

MDPI and ACS Style

Zakrzewska, M.; Opalinski, L.; Haugsten, E.M.; Otlewski, J.; Wiedlocha, A. Crosstalk between p38 and Erk 1/2 in Downregulation of FGF1-Induced Signaling. Int. J. Mol. Sci. 2019, 20, 1826.

Show more citation formats Show less citations formats

Note that from the first issue of 2016, MDPI journals use article numbers instead of page numbers. See further details here.

Related Articles

Article Metrics

Article Access Statistics

1

Comments

[Return to top]
Int. J. Mol. Sci. EISSN 1422-0067 Published by MDPI AG, Basel, Switzerland RSS E-Mail Table of Contents Alert
Back to Top