title: Activation of tyrosine phosphorylation in human T cells via the CD2 pathway. Regulation by the CD45 tyrosine phosphatase.
abstract: In this study we compare the effect of CD3 and CD2 ligation on tyrosine kinase activation in human peripheral blood T cells. Using antiphosphotyrosine antibody to detect tyrosine phosphorylation of cellular substrates, we demonstrate that mAb stimulation of either CD3 or CD2 results in tyrosine phosphorylation of the TCR-zeta chain and 135- and 100-kDa proteins. However, differences are observed between CD3 and CD2 ligation; only the former results in rapid tyrosine phosphorylation of 72-, 65-, and 40-kDa substrates. Co-aggregation of CD2 and CD45, a tyrosine phosphatase, results in inhibition of intracellular calcium elevation and T cell proliferation. We demonstrate in this study that this manipulation also inhibits polyphosphoinositide hydrolysis and tyrosine phosphorylation of the 100-kDa substrate. The failure of tyrosine phosphorylation of the 100-kDa substrate is specific in that phosphorylation of the 135-kDa protein is not inhibited. Similar results are observed when CD2 and CD45 are independently cross-linked rather than co-aggregated. The observation that CD45 cross-linking alters tyrosine phosphorylation of T cell substrates and effects polyphosphoinositide hydrolysis is further evidence that tyrosine phosphorylation regulates early events in T cell activation including, perhaps, phospholipase C activity.
authors.affiliation: Cell Biology and Metabolism Branch, National Institutes of Child Health and Human Development, Bethesda, MD 20892.
authors.forename: L E
authors.initials: LE
authors.lastname: Samelson
authors.forename: M C
authors.initials: MC
authors.lastname: Fletcher
authors.forename: J A
authors.initials: JA
authors.lastname: Ledbetter
authors.forename: C H
authors.initials: CH
authors.lastname: June
mesh_terms: D015703:Antigens, CD / Q000502:physiology*; D000943:Antigens, Differentiation / Q000502:physiology*; D000945:Antigens, Differentiation, T-Lymphocyte / Q000378:metabolism* / Q000502:physiology*; D018801:CD2 Antigens; D017252:CD3 Complex; D002118:Calcium / Q000502:physiology; D006649:Histocompatibility Antigens / Q000502:physiology*; D006801:Humans; D066298:In Vitro Techniques; D007295:Inositol Phosphates / Q000378:metabolism; D017493:Leukocyte Common Antigens; D008213:Lymphocyte Activation; D008970:Molecular Weight; D010749:Phosphoprotein Phosphatases / Q000378:metabolism*; D010766:Phosphorylation; D017027:Protein Tyrosine Phosphatases; D011505:Protein-Tyrosine Kinases / Q000378:metabolism*; D011940:Receptor Aggregation; D011948:Receptors, Antigen, T-Cell / Q000378:metabolism*; D011971:Receptors, Immunologic / Q000502:physiology*; D015398:Signal Transduction; D013601:T-Lymphocytes / Q000378:metabolism*; D013997:Time Factors; D010738:Type C Phospholipases / Q000502:physiology
chemical_list: D015703:Antigens, CD; D000943:Antigens, Differentiation; D000945:Antigens, Differentiation, T-Lymphocyte; D018801:CD2 Antigens; D017252:CD3 Complex; D006649:Histocompatibility Antigens; D007295:Inositol Phosphates; D011948:Receptors, Antigen, T-Cell; D011971:Receptors, Immunologic; D011505:Protein-Tyrosine Kinases; D010749:Phosphoprotein Phosphatases; D017493:Leukocyte Common Antigens; D017027:Protein Tyrosine Phosphatases; D010738:Type C Phospholipases; D002118:Calcium