title: Reconstitution of regulated phosphorylation of FcepsilonRI by a lipid raft-excluded protein-tyrosine phosphatase.
abstract: To examine the exquisite regulation of IgE-FcepsilonRI tyrosine phosphorylation by Lyn kinase that is stimulated by antigen-mediated cross-linking, we utilized co-expression of FcepsilonRI and Lyn in Chinese hamster ovary cells, which results in high basal levels of Lyn kinase activity and spontaneous phosphorylation of FcepsilonRI. We found that co-expression of a lipid raft-excluded transmembrane tyrosine phosphatase, PTPalpha, suppresses Lyn kinase activity and markedly reduces the level of spontaneous phosphorylation of FcepsilonRI, while facilitating its antigen-stimulated phosphorylation. Other tyrosine phosphatases, including SHP-1, CD45, and a lipid raft-preferring chimeric version of PTPalpha fail to reconstitute antigen-dependent FcepsilonRI phosphorylation. We concluded that both substrate specificity and submembrane location are critical to phosphatase-mediated regulation of Lyn kinase activity that supports activation of FcepsilonRI.
authors.affiliation: Department of Chemistry and Chemical Biology, Cornell University, Ithaca, New York 14853, USA.
authors.forename: Ryan M
authors.initials: RM
authors.lastname: Young
authors.forename: Xinmin
authors.initials: X
authors.lastname: Zheng
authors.forename: David
authors.initials: D
authors.lastname: Holowka
authors.forename: Barbara
authors.initials: B
authors.lastname: Baird
mesh_terms: D000818:Animals; D000941:Antigens / Q000276:immunology; D016466:CHO Cells; D006224:Cricetinae; D006801:Humans; D021962:Membrane Microdomains / Q000378:metabolism*; D010766:Phosphorylation; D017027:Protein Tyrosine Phosphatases / Q000235:genetics / Q000378:metabolism*; D017455:Receptors, IgE / Q000235:genetics / Q000276:immunology / Q000378:metabolism*; D015398:Signal Transduction; D013379:Substrate Specificity; D019061:src-Family Kinases / Q000235:genetics / Q000378:metabolism
chemical_list: D000941:Antigens; D017455:Receptors, IgE; C060902:lyn protein-tyrosine kinase; D019061:src-Family Kinases; D017027:Protein Tyrosine Phosphatases