Phosphorylation of fibroblast growth factor (FGF) receptor 1 at Ser777 by p38 mitogen-activated protein kinase regulates translocation of exogenous FGF1 to the cytosol and nucleus.

Molecular and Cellular Biology
Vigdis SørensenAntoni Wiedlocha

Abstract

Exogenous fibroblast growth factor 1 (FGF1) signals through activation of transmembrane FGF receptors (FGFRs) but may also regulate cellular processes after translocation to the cytosol and nucleus of target cells. Translocation of FGF1 occurs across the limiting membrane of intracellular vesicles and is a regulated process that depends on the C-terminal tail of the FGFR. Here, we report that translocation of FGF1 requires activity of the alpha isoform of p38 mitogen-activated protein kinase (MAPK). FGF1 translocation was inhibited after chemical inhibition of p38 MAPK or after small interfering RNA knockdown of p38alpha. Translocation was increased after stimulation of p38 MAPK with anisomycin, mannitol, or H2O2. The activity level of p38 MAPK was not found to affect endocytosis or intracellular sorting of FGF1/FGFR1. Instead, we found that p38 MAPK regulates FGF1 translocation by phosphorylation of FGFR1 at Ser777. The FGFR1 mutation S777A abolished FGF1 translocation, while phospho-mimetic mutations of Ser777 to Asp or Glu allowed translocation to take place and bypassed the requirement for active p38 MAPK. Ser777 in FGFR1 was directly phosphorylated by p38alpha in a cell-free system. These data demonstrate a crucial role fo...Continue Reading

References

Oct 1, 1987·Proceedings of the National Academy of Sciences of the United States of America·G BoucheF Amalric
Feb 28, 1994·Biochemical and Biophysical Research Communications·M GschwendtF Marks
Dec 22, 1995·The Journal of Biological Chemistry·A WiedłochaS Olsnes
Jan 19, 1996·The Journal of Biological Chemistry·S VainikkaK Alitalo
Aug 26, 2000·Cytokine & Growth Factor Reviews·B BoillyX Le Bourhis
Jul 30, 2002·The EMBO Journal·Camilla Skiple SkjerpenSjur Olsnes
Dec 31, 2002·Physiological Reviews·Sjur OlsnesAntoni Wiedłocha
Dec 6, 2003·Molecular Biology of the Cell·Jedrzej MałeckiSjur Olsnes
Feb 6, 2004·Nature Biotechnology·Angela ReynoldsAnastasia Khvorova
Jun 10, 2004·Microbiology and Molecular Biology Reviews : MMBR·Philippe P Roux, John Blenis
Oct 12, 2004·Trends in Genetics : TIG·Nobuyuki Itoh, David M Ornitz
Dec 3, 2004·Molecular Biology of the Cell·Antoni WiedłochaSjur Olsnes
Feb 3, 2005·Cell Research·Tyler Zarubin, Jiahuai Han
Mar 1, 2005·Nature Immunology·Jesus M SalvadorJonathan D Ashwell
May 3, 2005·Cytokine & Growth Factor Reviews·V P EswarakumarJ Schlessinger
Aug 11, 2005·Journal of Cell Science·Ellen Margrethe HaugstenJørgen Wesche
Aug 30, 2005·Journal of Molecular Biology·Malgorzata ZakrzewskaJacek Otlewski
Sep 3, 2005·The EMBO Journal·Gaëtane MacéAngel R Nebreda
Sep 13, 2005·Journal of Cellular Physiology·Mitla Garcia-MayaJane L Saffell
Oct 18, 2005·Molecular and Cellular Biology·Zhi ShengWilliam J Chirico
Feb 24, 2006·The Journal of Biological Chemistry·Jørgen WescheSjur Olsnes
Apr 15, 2006·BioEssays : News and Reviews in Molecular, Cellular and Developmental Biology·Vigdis SørensenAntoni Wiedłocha

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Citations

Jul 4, 2009·The Journal of Biological Chemistry·Malgorzata ZakrzewskaSjur Olsnes
Feb 14, 2013·Science Signaling·Malgorzata ZakrzewskaAntoni Wiedlocha
Oct 22, 2013·Oncogene·B Nadratowska-WesolowskaA Wiedlocha
Jul 25, 2015·The American Journal of Chinese Medicine·Shang-Min ChouTsai-Kun Li
Aug 16, 2011·Biochimica Et Biophysica Acta·Lijuan He, Kalina Hristova
Jul 16, 2010·The Biochemical Journal·Ana Cuadrado, Angel R Nebreda
Sep 27, 2016·Scientific Reports·B Z CamurdanogluR Herbst
Mar 5, 2019·Anti-cancer Agents in Medicinal Chemistry·Habib ZarredarMilad Asadi
May 21, 2009·The Journal of Immunology : Official Journal of the American Association of Immunologists·Srivatsava NaiduStephan Immenschuh
Jan 28, 2014·Molecular Biology Reports·Fulya DoğanerCengiz Bal
Jul 4, 2018·Materials·Megane Beldjilali-LabroCécile Legallais
Jul 2, 2020·Cell and Tissue Research·Na ShangWood Yee Chan
Apr 25, 2019·International Journal of Molecular Sciences·Malgorzata ZakrzewskaAntoni Wiedlocha
Jun 2, 2020·Cytokine & Growth Factor Reviews·Katarzyna Dominika SluzalskaMalgorzata Zakrzewska
Jul 3, 2021·International Journal of Molecular Sciences·Azzurra Margiotta
Dec 8, 2021·Journal of Orofacial Orthopedics = Fortschritte Der Kieferorthopädie : Organ/official Journal Deutsche Gesellschaft Für Kieferorthopädie·Isabel KnaupMichael Wolf

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