Regulation of the low molecular weight phosphotyrosine phosphatase by phosphorylation at tyrosines 131 and 132

J Biol Chem. 1997 Feb 28;272(9):5371-4. doi: 10.1074/jbc.272.9.5371.

Abstract

Activation of resting T lymphocytes is initiated by rapid but transient tyrosine phosphorylation of a number of cellular proteins. Several protein tyrosine kinases and protein tyrosine phosphatases are known to be important for this response. Here we report that normal T lymphocytes express the B isoform of low molecular weight protein tyrosine phosphatase B (LMPTP-B). The cDNA was cloned from Jurkat T cells, and an antiserum was raised against it. LMPTP immunoprecipitated from resting Jurkat T cells was found to be tyrosine phosphorylated. On stimulation of the cells through their T cell antigen receptor, the phosphotyrosine content of LMPTP-B declined rapidly. In co-transfected COS cells, Lck and Fyn caused phosphorylation of LMPTP, whereas Csk, Zap, and Jak2 did not. Most of the phosphate was located at Tyr-131, and some was also located at Tyr-132. Incubation of wild-type LMPTP with Lck and adenosine 5'-O-(thiotriphosphate) caused a 2-fold increase in the activity of LMPTP. Site-directed mutagenesis showed that Tyr-131 is important for the catalytic activity of LMPTP, and that thiophosphorylation of Tyr-131, and to a lesser degree Tyr-132, is responsible for the activation.

Publication types

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

MeSH terms

  • 3T3 Cells
  • Animals
  • Binding Sites
  • COS Cells
  • Cloning, Molecular
  • Enzyme Activation
  • Humans
  • Isoenzymes / genetics
  • Isoenzymes / metabolism*
  • Jurkat Cells
  • Kinetics
  • Lymphocyte Activation*
  • Lymphocyte Specific Protein Tyrosine Kinase p56(lck)
  • Mice
  • Molecular Weight
  • Mutagenesis
  • Oncogene Proteins, Viral / metabolism
  • Phosphorylation
  • Polymerase Chain Reaction
  • Protein Tyrosine Phosphatases / genetics
  • Protein Tyrosine Phosphatases / metabolism*
  • Structure-Activity Relationship
  • T-Lymphocytes / enzymology*
  • Tyrosine / metabolism*
  • src-Family Kinases / metabolism

Substances

  • Isoenzymes
  • Oncogene Proteins, Viral
  • Tyrosine
  • Lymphocyte Specific Protein Tyrosine Kinase p56(lck)
  • src-Family Kinases
  • Protein Tyrosine Phosphatases