title: Regulation of the tyrosine phosphorylation of Phospholipid Scramblase 1 in mast cells that are stimulated through the high-affinity IgE receptor.
abstract: Engagement of high-affinity immunoglobulin E receptors (FcεRI) activates two signaling pathways in mast cells. The Lyn pathway leads to recruitment of Syk and to calcium mobilization whereas the Fyn pathway leads to phosphatidylinositol 3-kinase recruitment. Mapping the connections between both pathways remains an important task to be completed. We previously reported that Phospholipid Scramblase 1 (PLSCR1) is phosphorylated on tyrosine after cross-linking FcεRI on RBL-2H3 rat mast cells, amplifies mast cell degranulation, and is associated with both Lyn and Syk tyrosine kinases. Here, analysis of the pathway leading to PLSCR1 tyrosine phosphorylation reveals that it depends on the FcRγ chain. FcεRI aggregation in Fyn-deficient mouse bone marrow-derived mast cells (BMMC) induced a more robust increase in FcεRI-dependent tyrosine phosphorylation of PLSCR1 compared to wild-type cells, whereas PLSCR1 phosphorylation was abolished in Lyn-deficient BMMC. Lyn association with PLSCR1 was not altered in Fyn-deficient BMMC. PLSCR1 phosphorylation was also dependent on the kinase Syk and significantly, but partially, dependent on detectable calcium mobilization. Thus, the Lyn/Syk/calcium axis promotes PLSCR1 phosphorylation in multiple ways. Conversely, the Fyn-dependent pathway negatively regulates it. This study reveals a complex regulation for PLSCR1 tyrosine phosphorylation in FcεRI-activated mast cells and that PLSCR1 sits at a crossroads between Lyn and Fyn pathways.
authors.affiliation: INSERM U1149, Faculté de Médecine Xavier Bichat, Paris, France; University Paris-Diderot, Sorbonne Paris Cité, Laboratoire d'excellence INFLAMEX, DHU FIRE, Paris, France.
authors.forename: Asma
authors.initials: A
authors.lastname: Kassas
authors.affiliation: INSERM U1149, Faculté de Médecine Xavier Bichat, Paris, France; University Paris-Diderot, Sorbonne Paris Cité, Laboratoire d'excellence INFLAMEX, DHU FIRE, Paris, France.
authors.forename: Ivan C
authors.initials: IC
authors.lastname: Moura
authors.affiliation: Laboratory of Molecular Immunogenetics, Molecular Immunology and Inflammation Branch, NIAMSD, NIH, Bethesda, Maryland, United States of America.
authors.forename: Yumi
authors.initials: Y
authors.lastname: Yamashita
authors.affiliation: Laboratory of Molecular Immunogenetics, Molecular Immunology and Inflammation Branch, NIAMSD, NIH, Bethesda, Maryland, United States of America.
authors.forename: Jorg
authors.initials: J
authors.lastname: Scheffel
authors.affiliation: INSERM U1149, Faculté de Médecine Xavier Bichat, Paris, France; University Paris-Diderot, Sorbonne Paris Cité, Laboratoire d'excellence INFLAMEX, DHU FIRE, Paris, France.
authors.forename: Claudine
authors.initials: C
authors.lastname: Guérin-Marchand
authors.affiliation: INSERM U1149, Faculté de Médecine Xavier Bichat, Paris, France; University Paris-Diderot, Sorbonne Paris Cité, Laboratoire d'excellence INFLAMEX, DHU FIRE, Paris, France.
authors.forename: Ulrich
authors.initials: U
authors.lastname: Blank
authors.affiliation: Department of Medicine, University of Rochester School of Medicine and Dentistry, Rochester, New York, United States of America.
authors.forename: Peter J
authors.initials: PJ
authors.lastname: Sims
authors.affiliation: Department of Medicine, University of Rochester School of Medicine and Dentistry, Rochester, New York, United States of America.
authors.forename: Therese
authors.initials: T
authors.lastname: Wiedmer
authors.affiliation: INSERM U1149, Faculté de Médecine Xavier Bichat, Paris, France; University Paris-Diderot, Sorbonne Paris Cité, Laboratoire d'excellence INFLAMEX, DHU FIRE, Paris, France.
authors.forename: Renato C
authors.initials: RC
authors.lastname: Monteiro
authors.affiliation: Laboratory of Molecular Immunogenetics, Molecular Immunology and Inflammation Branch, NIAMSD, NIH, Bethesda, Maryland, United States of America.
authors.forename: Juan
authors.initials: J
authors.lastname: Rivera
authors.affiliation: INSERM U1149, Faculté de Médecine Xavier Bichat, Paris, France; University Paris-Diderot, Sorbonne Paris Cité, Laboratoire d'excellence INFLAMEX, DHU FIRE, Paris, France.
authors.forename: Nicolas
authors.initials: N
authors.lastname: Charles
authors.affiliation: INSERM U1149, Faculté de Médecine Xavier Bichat, Paris, France; University Paris-Diderot, Sorbonne Paris Cité, Laboratoire d'excellence INFLAMEX, DHU FIRE, Paris, France.
authors.forename: Marc
authors.initials: M
authors.lastname: Benhamou
mesh_terms: D000818:Animals; D002118:Calcium / Q000378:metabolism; D015550:Cell Degranulation / Q000276:immunology; D002460:Cell Line; D005786:Gene Expression Regulation; D047908:Intracellular Signaling Peptides and Proteins / Q000235:genetics / Q000276:immunology*; D008407:Mast Cells / Q000166:cytology / Q000276:immunology*; D051379:Mice; D019869:Phosphatidylinositol 3-Kinases / Q000235:genetics / Q000276:immunology; D049294:Phospholipid Transfer Proteins / Q000235:genetics / Q000276:immunology*; D010766:Phosphorylation; D011505:Protein-Tyrosine Kinases / Q000235:genetics / Q000276:immunology*; D051076:Proto-Oncogene Proteins c-fyn / Q000235:genetics / Q000276:immunology*; D051381:Rats; D017455:Receptors, IgE / Q000235:genetics / Q000276:immunology*; D015398:Signal Transduction; D000072377:Syk Kinase; D014443:Tyrosine / Q000378:metabolism; D019061:src-Family Kinases / Q000235:genetics / Q000276:immunology*
chemical_list: C521907:Fc-epsilon receptor I beta-chain, mouse; D047908:Intracellular Signaling Peptides and Proteins; D049294:Phospholipid Transfer Proteins; C493426:Plscr1 protein, mouse; D017455:Receptors, IgE; D014443:Tyrosine; D019869:Phosphatidylinositol 3-Kinases; D011505:Protein-Tyrosine Kinases; C494960:Fyn protein, mouse; D051076:Proto-Oncogene Proteins c-fyn; D000072377:Syk Kinase; C000606897:Syk protein, mouse; C000606898:Syk protein, rat; C060902:lyn protein-tyrosine kinase; D019061:src-Family Kinases; D002118:Calcium