The CD28 and CTLA-4 receptors associate with the serine/threonine phosphatase PP2A.
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.
Chuang
E
E
Gwen Knapp Center for Lupus and Immunobiology Research, University of Chicago, Illinois 60637, USA.
Fisher
T S
TS
Morgan
R W
RW
Robbins
M D
MD
Duerr
J M
JM
Vander Heiden
M G
MG
Gardner
J P
JP
Hambor
J E
JE
Neveu
M J
MJ
Thompson
C B
CB
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
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