LAT is required for TCR-mediated activation of PLCgamma1 and the Ras pathway.
In this study, we present the further characterization of a mutant Jurkat T cell line, J.CaM2, that is defective in TCR-mediated signal transduction. Although initial TCR-mediated signaling events such as the inducible tyrosine phosphorylation of the TCR-zeta chain and ZAP-70 are intact in J.CaM2, subsequent events, including increases in intracellular calcium, Ras activation, and IL-2 gene expression are defective. Subsequent analysis of J.CaM2 demonstrated a severe deficiency in pp36/LAT expression, a recently cloned adaptor protein implicated in TCR signaling. Importantly, reexpression of LAT in J.CaM2 restored all aspects of TCR signaling. These results demonstrate a necessary and exclusive role for LAT in T cell activation.
Finco
T S
TS
Department of Medicine, The Howard Hughes Medical Institute, University of California at San Francisco, 94143, USA.
Kadlecek
T
T
Zhang
W
W
Samelson
L E
LE
Weiss
A
A
D048868:Adaptor Proteins, Signal Transducing; D015703:Antigens, CD / Q000096:biosynthesis; D000945:Antigens, Differentiation, T-Lymphocyte / Q000096:biosynthesis; D002118:Calcium / Q000378:metabolism; D017871:Calcium-Calmodulin-Dependent Protein Kinases / Q000378:metabolism; D002352:Carrier Proteins / Q000502:physiology*; D004268:DNA-Binding Proteins / Q000502:physiology; D004789:Enzyme Activation / Q000502:physiology; D005786:Gene Expression Regulation / Q000502:physiology; D006801:Humans; D007376:Interleukin-2 / Q000096:biosynthesis / Q000235:genetics; D007527:Isoenzymes / Q000378:metabolism*; D019169:Jurkat Cells / Q000201:enzymology / Q000378:metabolism; D037181:Lectins, C-Type; D008565:Membrane Proteins; D009154:Mutation; D050778:NFATC Transcription Factors; D009687:Nuclear Proteins; D051966:Phospholipase C gamma; D010750:Phosphoproteins / Q000378:metabolism / Q000502:physiology*; D010766:Phosphorylation; D011505:Protein-Tyrosine Kinases / Q000378:metabolism; D011948:Receptors, Antigen, T-Cell / Q000502:physiology*; D015398:Signal Transduction / Q000502:physiology*; D018808:Transcription Factor AP-1 / Q000502:physiology; D014157:Transcription Factors / Q000502:physiology; D010738:Type C Phospholipases / Q000378:metabolism*; D014443:Tyrosine / Q000378:metabolism; D051746:ZAP-70 Protein-Tyrosine Kinase; D018631:ras Proteins / Q000502:physiology*; D000099192:CD69 Antigens
D048868:Adaptor Proteins, Signal Transducing; D015703:Antigens, CD; D000945:Antigens, Differentiation, T-Lymphocyte; D002118:Calcium; D017871:Calcium-Calmodulin-Dependent Protein Kinases; D002352:Carrier Proteins; D004268:DNA-Binding Proteins; D007376:Interleukin-2; D007527:Isoenzymes; D037181:Lectins, C-Type; D008565:Membrane Proteins; D050778:NFATC Transcription Factors; D009687:Nuclear Proteins; D051966:Phospholipase C gamma; D010750:Phosphoproteins; D011505:Protein-Tyrosine Kinases; D011948:Receptors, Antigen, T-Cell; D018808:Transcription Factor AP-1; D014157:Transcription Factors; D010738:Type C Phospholipases; D014443:Tyrosine; D051746:ZAP-70 Protein-Tyrosine Kinase; D018631:ras Proteins; D000099192:CD69 Antigens; C110810:LAT protein, human; C092947:SLP-76 signal Transducing adaptor proteins; C497261:ZAP70 protein, human