LAT is required for TCR-mediated activation of PLCgamma1 and the Ras pathway

Immunity. 1998 Nov;9(5):617-26. doi: 10.1016/s1074-7613(00)80659-7.

Abstract

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.

Publication types

  • Research Support, U.S. Gov't, P.H.S.

MeSH terms

  • Adaptor Proteins, Signal Transducing*
  • Antigens, CD / biosynthesis
  • Antigens, Differentiation, T-Lymphocyte / biosynthesis
  • Calcium / metabolism
  • Calcium-Calmodulin-Dependent Protein Kinases / metabolism
  • Carrier Proteins / physiology*
  • DNA-Binding Proteins / physiology
  • Enzyme Activation / physiology
  • Gene Expression Regulation / physiology
  • Humans
  • Interleukin-2 / biosynthesis
  • Interleukin-2 / genetics
  • Isoenzymes / metabolism*
  • Jurkat Cells / enzymology
  • Jurkat Cells / metabolism
  • Lectins, C-Type
  • Membrane Proteins*
  • Mutation
  • NFATC Transcription Factors
  • Nuclear Proteins*
  • Phospholipase C gamma
  • Phosphoproteins / metabolism
  • Phosphoproteins / physiology*
  • Phosphorylation
  • Protein-Tyrosine Kinases / metabolism
  • Receptors, Antigen, T-Cell / physiology*
  • Signal Transduction / physiology*
  • Transcription Factor AP-1 / physiology
  • Transcription Factors / physiology
  • Type C Phospholipases / metabolism*
  • Tyrosine / metabolism
  • ZAP-70 Protein-Tyrosine Kinase
  • ras Proteins / physiology*

Substances

  • Adaptor Proteins, Signal Transducing
  • Antigens, CD
  • Antigens, Differentiation, T-Lymphocyte
  • CD69 antigen
  • Carrier Proteins
  • DNA-Binding Proteins
  • Interleukin-2
  • Isoenzymes
  • LAT protein, human
  • Lectins, C-Type
  • Membrane Proteins
  • NFATC Transcription Factors
  • Nuclear Proteins
  • Phosphoproteins
  • Receptors, Antigen, T-Cell
  • SLP-76 signal Transducing adaptor proteins
  • Transcription Factor AP-1
  • Transcription Factors
  • Tyrosine
  • Protein-Tyrosine Kinases
  • ZAP-70 Protein-Tyrosine Kinase
  • ZAP70 protein, human
  • Calcium-Calmodulin-Dependent Protein Kinases
  • Type C Phospholipases
  • Phospholipase C gamma
  • ras Proteins
  • Calcium