title: Role of two adaptor molecules SLP-76 and LAT in the PI3K signaling pathway in activated T cells.
abstract: Previously, we identified p85, a subunit of PI3K, as one of the molecules that interacts with the N-terminal region of Src homology 2 domain-containing leukocyte protein of 76 kDa (SLP-76). We also demonstrated that tyrosine phosphorylation either at the 113 and/or 128 position is sufficient for the association of SLP-76 with the Src homology 2 domain near the N terminus of p85. The present study further examines the role of the association of these two molecules on the activation of PI3K signaling cascade. Experiments were done to determine the role of SLP-76, either wild-type, tyrosine mutants, or membrane-targeted forms of various SLP-76 constructs, on the membrane localization and phosphorylation of Akt, which is an event downstream of PI3K activation. Reconstitution studies with these various SLP-76 constructs in a Jurkat variant cell line that lacks SLP-76 or linker for activation of T cells (LAT) show that the activation of PI3K pathway following TCR ligation requires both SLP-76 and LAT adaptor proteins. The results suggest that SLP-76 associates with p85 after T cell activation and that LAT recruits this complex to the membrane, leading to Akt activation.
authors.affiliation: Division of Life and Pharmaceutical Sciences, Ewha Womans University, Seoul 120-750, Korea.
authors.forename: Eun Kyung
authors.initials: EK
authors.lastname: Shim
authors.forename: Seung Hee
authors.initials: SH
authors.lastname: Jung
authors.forename: Jong Ran
authors.initials: JR
authors.lastname: Lee
mesh_terms: D048868:Adaptor Proteins, Signal Transducing / Q000378:metabolism / Q000502:physiology*; D002462:Cell Membrane / Q000201:enzymology / Q000276:immunology / Q000378:metabolism; D004789:Enzyme Activation / Q000276:immunology; D006801:Humans; D019169:Jurkat Cells; D008213:Lymphocyte Activation / Q000276:immunology*; D008565:Membrane Proteins / Q000378:metabolism / Q000502:physiology*; D051058:Oncogene Protein v-akt / Q000378:metabolism; D019869:Phosphatidylinositol 3-Kinases / Q000378:metabolism / Q000502:physiology*; D010750:Phosphoproteins / Q000378:metabolism / Q000502:physiology*; D010766:Phosphorylation / Q000276:immunology; D021122:Protein Subunits / Q000378:metabolism / Q000502:physiology*; D021381:Protein Transport / Q000276:immunology; D011948:Receptors, Antigen, T-Cell / Q000378:metabolism / Q000502:physiology; D015398:Signal Transduction / Q000276:immunology*; D016176:T-Lymphocyte Subsets / Q000201:enzymology / Q000276:immunology* / Q000378:metabolism*
chemical_list: D048868:Adaptor Proteins, Signal Transducing; C110810:LAT protein, human; D008565:Membrane Proteins; D010750:Phosphoproteins; D021122:Protein Subunits; D011948:Receptors, Antigen, T-Cell; C092947:SLP-76 signal Transducing adaptor proteins; D019869:Phosphatidylinositol 3-Kinases; D051058:Oncogene Protein v-akt