title: The CD28 and CTLA-4 receptors associate with the serine/threonine phosphatase PP2A.
abstract: CD28 and CTLA-4 are related members of a family of T lymphocyte cell surface receptors that function to regulate T cell activation. We have found that the cytoplasmic domains of both CTLA-4 and CD28 can associate with members of the PP2A family of serine/threonine phosphatases. The association of PP2A with CD28 was negatively regulated by tyrosine phosphorylation of the CD28 cytoplasmic domain. Inhibition of PP2A activity in Jurkat leukemia T cells by treatment with okadaic acid or by expression of a dominant-negative mutant enhanced T cell activation induced by CD28 engagement. Interactions between cell surface receptors such as CTLA-4 and CD28 and serine/threonine phosphatases may represent a novel mechanism for modulating the intracellular signal transduction pathways associated with cell activation.
authors.affiliation: Gwen Knapp Center for Lupus and Immunobiology Research, University of Chicago, Illinois 60637, USA.
authors.forename: E
authors.initials: E
authors.lastname: Chuang
authors.forename: T S
authors.initials: TS
authors.lastname: Fisher
authors.forename: R W
authors.initials: RW
authors.lastname: Morgan
authors.forename: M D
authors.initials: MD
authors.lastname: Robbins
authors.forename: J M
authors.initials: JM
authors.lastname: Duerr
authors.forename: M G
authors.initials: MG
authors.lastname: Vander Heiden
authors.forename: J P
authors.initials: JP
authors.lastname: Gardner
authors.forename: J E
authors.initials: JE
authors.lastname: Hambor
authors.forename: M J
authors.initials: MJ
authors.lastname: Neveu
authors.forename: C B
authors.initials: CB
authors.lastname: Thompson
mesh_terms: D000069594:Abatacept; D000595:Amino Acid Sequence; D015703:Antigens, CD; D000943:Antigens, Differentiation / Q000378:metabolism*; D018106:CD28 Antigens / Q000378:metabolism* / Q000502:physiology; D060908:CTLA-4 Antigen; D002460:Cell Line; D003593:Cytoplasm / Q000276:immunology / Q000378:metabolism; D015536:Down-Regulation; D004789:Enzyme Activation / Q000187:drug effects / Q000276:immunology; D020035:Holoenzymes / Q000276:immunology / Q000378:metabolism; D006801:Humans; D018796:Immunoconjugates; D007376:Interleukin-2 / Q000037:antagonists & inhibitors / Q000096:biosynthesis; D019169:Jurkat Cells / Q000187:drug effects / Q000201:enzymology / Q000276:immunology / Q000378:metabolism; D019860:Lymphocyte Specific Protein Tyrosine Kinase p56(lck) / Q000502:physiology; D008969:Molecular Sequence Data; D019319:Okadaic Acid / Q000494:pharmacology; D010446:Peptide Fragments / Q000276:immunology / Q000378:metabolism; D010749:Phosphoprotein Phosphatases / Q000037:antagonists & inhibitors / Q000378:metabolism*; D017434:Protein Structure, Tertiary; D011956:Receptors, Cell Surface / Q000378:metabolism*; D013601:T-Lymphocytes / Q000187:drug effects / Q000201:enzymology / Q000378:metabolism
chemical_list: D015703:Antigens, CD; D000943:Antigens, Differentiation; D018106:CD28 Antigens; D060908:CTLA-4 Antigen; C556706:CTLA4 protein, human; D020035:Holoenzymes; D018796:Immunoconjugates; D007376:Interleukin-2; D010446:Peptide Fragments; D011956:Receptors, Cell Surface; D019319:Okadaic Acid; D000069594:Abatacept; D019860:Lymphocyte Specific Protein Tyrosine Kinase p56(lck); D010749:Phosphoprotein Phosphatases