PI3 kinase function is vital for the function but not formation of LAT-mediated signaling complexes.
The induction of the T cell receptor (TCR) is necessary for the activation and function of human T cells. TCR activation results in the tyrosine phosphorylation of LAT, leading to the direct interaction with several proteins, including PLC-gamma 1, Grb2 and Gads. These direct ligands then mediate the indirect interaction of LAT with proteins, such as SLP-76, Vav1 and Itk. PLC-gamma 1, Vav1 and Itk contain pleckstrin homology (PH) domains that interact with the enzymatic product of phosphoinositide-3-kinase (PI3K), suggesting the function of PI3K may modulate LAT-mediated complexes. Therefore, we characterized the poorly understood role of PI3K activity in the formation and function of multiprotein signaling complexes that form at LAT. Inhibition of PI3K catalytic function had little effect on the phosphorylation of LAT, SLP-76, Vav1 or PLC-gamma 1 or on the ability of PLC-gamma 1 to interact with LAT or SLP-76. However, PI3K activity appeared to be required for the induction of downstream signaling events. These data indicate that the formation of LAT-mediated complexes do not appear to depend on PI3K activity, whereas the optimal downstream function of these complexes requires the catalytic function of PI3K.
Department of Microbiology, Carver College of Medicine, University of Iowa, Iowa City, IA 52242, USA.
Noemi
N
Cruz-Orcutt
Jon C D
JC
Houtman
D048868:Adaptor Proteins, Signal Transducing / Q000378:metabolism / Q000502:physiology*; D002460:Cell Line; D006801:Humans; D008565:Membrane Proteins / Q000502:physiology*; D046912:Multiprotein Complexes / Q000502:physiology; D019869:Phosphatidylinositol 3-Kinases / Q000502:physiology*; D000081082:Phosphoinositide-3 Kinase Inhibitors; D051966:Phospholipase C gamma / Q000276:immunology / Q000378:metabolism; D010750:Phosphoproteins / Q000378:metabolism; D010766:Phosphorylation; D011485:Protein Binding; D051567:Proto-Oncogene Proteins c-vav / Q000378:metabolism; D011948:Receptors, Antigen, T-Cell / Q000502:physiology; D015398:Signal Transduction; D013601:T-Lymphocytes / Q000378:metabolism
D048868:Adaptor Proteins, Signal Transducing; D008565:Membrane Proteins; D046912:Multiprotein Complexes; D019869:Phosphatidylinositol 3-Kinases; D000081082:Phosphoinositide-3 Kinase Inhibitors; D051966:Phospholipase C gamma; D010750:Phosphoproteins; D051567:Proto-Oncogene Proteins c-vav; D011948:Receptors, Antigen, T-Cell; C110810:LAT protein, human; C092947:SLP-76 signal Transducing adaptor proteins; C496618:VAV1 protein, human