The CD28 and CTLA-4 Receptors Associate with the Serine/Threonine Phosphatase PP2A

• Published in: Immunity (Cambridge, Mass.) Mass.), 2000-09, Vol.13 (3), p.313-322
• Main Authors: Chuang, Ellen, Fisher, Timothy S., Morgan, Rodney W., Robbins, Michael D., Duerr, James M., Vander Heiden, Matthew G., Gardner, Joseph P., Hambor, John E., Neveu, Mark J., Thompson, Craig B.
• Format: Article
• Language: English
• Subjects: Abatacept; Amino Acid Sequence; Antigens, CD; Antigens, Differentiation - metabolism; CD28 antigen; CD28 Antigens - metabolism; CD28 Antigens - physiology; Cell Line; CTLA-4 Antigen; CTLA-4 protein; Cytoplasm - immunology; Cytoplasm - metabolism; Down-Regulation; Enzyme Activation - drug effects; Enzyme Activation - immunology; Holoenzymes - immunology; Holoenzymes - metabolism; Humans; Immunoconjugates; Interleukin-2 - antagonists & inhibitors; Interleukin-2 - biosynthesis; Jurkat Cells - drug effects; Jurkat Cells - enzymology; Jurkat Cells - immunology; Jurkat Cells - metabolism; Lymphocyte Specific Protein Tyrosine Kinase p56(lck) - physiology; Molecular Sequence Data; Okadaic Acid - pharmacology; Peptide Fragments - immunology; Peptide Fragments - metabolism; Phosphoprotein Phosphatases - antagonists & inhibitors; Phosphoprotein Phosphatases - metabolism; Protein Structure, Tertiary; protein-serine/threonine phosphatase; Receptors, Cell Surface - metabolism; T-Lymphocytes - drug effects; T-Lymphocytes - enzymology; T-Lymphocytes - metabolism
• ISSN: 1074-7613; 1097-4180
• DOI: 10.1016/S1074-7613(00)00031-5

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.