Differential dephosphorylation of the FcRgamma immunoreceptor tyrosine-based activation motif tyrosines with dissimilar potential for activating Syk.

The Journal of Biological Chemistry
Toshiyuki YamashitaJuan Rivera

Abstract

The cell surface-expressed gamma chain of the high affinity receptor for IgE (FcepsilonRI) can be phosphorylated on two tyrosine residues of the immunoreceptor tyrosine-based activation motif (ITAM), leading to recruitment and activation of spleen tyrosine kinase (Syk), a kinase that is essential for mast cell signaling and allergic responses. However, it is not known whether preferential phosphorylation or dephosphorylation of the two individual FcRgamma tyrosines (the N-terminal Tyr47 and C-terminal Tyr58) could regulate Syk activation. Herein we report that phosphorylation of only Tyr58 was able to elicit Syk phosphorylation and a weak rise in intracellular calcium, suggesting that Tyr58 phosphorylation may be distinctively important for Syk activation. In vitro and in vivo studies revealed that both Tyr47 and Tyr58 could be similarly phosphorylated. However, mass spectrometric analysis of the phosphorylated FcepsilonRgamma from bone marrow-derived mast cells showed that phosphorylation at Tyr47 was at least 2-fold greater than at Tyr58. This suggested that, once phosphorylated, Tyr58 is preferentially dephosphorylated. In vitro studies demonstrated more efficient dephosphorylation of Tyr58 (by the receptor-associated phosph...Continue Reading

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Citations

May 21, 2013·Current Opinion in Immunology·Yacine BounabMarc Daëron
May 9, 2012·The Journal of Allergy and Clinical Immunology·Riccardo SibilanoCarlo E Pucillo
Sep 1, 2017·Molecular Biology of the Cell·Samantha L SchwartzDiane S Lidke
Oct 28, 2016·Nature Communications·Kwok Ho YipMichele A Grimbaldeston
Mar 18, 2009·Immunological Reviews·Alasdair M Gilfillan, Juan Rivera
Jun 20, 2019·Molecular Biology of the Cell·Timothy TraversS Gnanakaran
Mar 24, 2010·The Journal of Immunology : Official Journal of the American Association of Immunologists·Damiana Alvarez-ErricoJuan Rivera
Mar 21, 2012·The Journal of Immunology : Official Journal of the American Association of Immunologists·Satoshi NunomuraChisei Ra
May 12, 2019·The Journal of Immunology : Official Journal of the American Association of Immunologists·S Elizabeth FranksJohn C Cambier
Oct 27, 2015·Immunological Reviews·Andrew Getahun, John C Cambier
Feb 1, 2014·Molecular and Cellular Biochemistry·Naveen BojjireddyGosukonda Subrahmanyam

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