title: Phosphorylation abnormalities: NZB mice exhibit a B-cell signalling defect.
abstract: NZB mice demonstrate common and consistent abnormalities in B-cell activation and signalling. One of the hallmark characteristics of lupus disease is the prevalent hypergammaglobulinaemia, composed primarily of anti-nuclear antibodies. In addition to the hyperproliferation seen in mice exhibiting disease, the B cells also demonstrate a marked degree of hyperactivity in response to B-cell receptor occupancy. This points to an intrinsic defect in the signalling pathways regulating the response to an activation event. Correspondingly, B cells of NZB mice exhibit a significant lack of phosphatase activity, both at baseline and in response to stimulation. This is directly reflected by a higher level of phosphorylation of tyrosine residues. Individually, SAPK and SHIP-1, both players in the B-cell receptor signalling cascade, are also found to be abnormally phosphorylated in the NZB mouse.
authors.affiliation: Department of Hematology, University of California at Davis Medical Center, Sacramento, CA 95817, USA.
authors.forename: Joseph M
authors.initials: JM
authors.lastname: Tuscano
authors.forename: Tom C
authors.initials: TC
authors.lastname: Hsu
authors.forename: Hayes
authors.initials: H
authors.lastname: McKnight
authors.forename: Aftab A
authors.initials: AA
authors.lastname: Ansari
authors.forename: M Eric
authors.initials: ME
authors.lastname: Gershwin
mesh_terms: D000818:Animals; D001402:B-Lymphocytes / Q000502:physiology*; D051379:Mice; D008814:Mice, Inbred NZB; D020928:Mitogen-Activated Protein Kinases / Q000172:deficiency* / Q000378:metabolism; D010766:Phosphorylation; D011947:Receptors, Antigen, B-Cell / Q000172:deficiency / Q000235:genetics; D015398:Signal Transduction / Q000502:physiology*
chemical_list: D011947:Receptors, Antigen, B-Cell; D020928:Mitogen-Activated Protein Kinases