       Document 0403
 DOCN  M9610403
 TI    Modulation of the Grb2-associated protein complex in human CD4+ T cells
       by receptor activation.
 DT    9601
 AU    Lahesmaa R; Allsup A; Soderberg C; Jackman J; Findell P; Peltz G;
       Department of Leukocyte Biology, Syntex Research, Palo Alto, CA; 94303,
       USA.
 SO    J Immunol. 1995 Oct 15;155(8):3815-22. Unique Identifier : AIDSLINE
       MED/96003420
 AB    A panel of human CD4+ T cell clones was utilized to dissect and analyze
       the biochemical consequences of activation of CD3 or CD28. To
       molecularly characterize receptor-activated proximal signaling events,
       tyrosine-phosphorylated proteins co-precipitating with a Grb2 fusion
       protein after receptor activation were analyzed. Ligation of CD28, but
       not other costimulatory molecules, induced the tyrosine phosphorylation
       of two previously identified Grb2 binding proteins (pp76 and pp116). A
       third Grb2 binding protein (pp36) was extensively tyrosine
       phosphophorylated in response to combined CD3 and CD28 activation, but
       not in response to ligation of either receptor alone. cAMP and
       co-ligation of CD45 affected the receptor-activated tyrosine
       phosphorylation of Grb2-associated proteins. Furthermore, we
       demonstrated that two signaling molecules, Vav and phosphatidylinositol
       3'-kinase (PI(3)K), also interacted with the Grb2 protein complex. The
       activity of PI(3)K was required for T cell activation, because
       wortmannin, a PI(3)K inhibitor, blocked T cell proliferation and
       cytokine production induced by ligation of CD3 and CD28. In conclusion,
       we demonstrate that in activated human T cell clones, the composition of
       Grb2 protein complex is modulated by costimulatory signals and cAMP,
       which may be important for the regulation of intracellular signal
       transduction.
 DE    Clone Cells  Cyclic AMP/PHYSIOLOGY  CD4-Positive
       T-Lymphocytes/*IMMUNOLOGY  Human  Lymphocyte Transformation
       Proteins/*METABOLISM  Receptors, Antigen, T-Cell/*PHYSIOLOGY  Receptors,
       Epidermal Growth Factor-Urogastrone/*METABOLISM  Signal Transduction
       Th1 Cells/IMMUNOLOGY  JOURNAL ARTICLE

       SOURCE: National Library of Medicine.  NOTICE: This material may be
       protected by Copyright Law (Title 17, U.S.Code).

