Surface expression of hemopoietic cell phosphatase fails to complement CD45 deficiency and inhibits TCR-mediated signal transduction in a Jurkat T cell clone.
Previous studies have shown that the protein tyrosine phosphatase CD45 is required for initiation of signal transduction through several lymphoid receptors. In contrast, there is increasing evidence that another protein tyrosine phosphatase, hemopoietic cell phosphatase (known as HCP, SHP, PTP1C, SHPTP-1, or PTPN6), is a negative regulator of signaling in hemopoietic cells. To determine the effect of HCP on signal transduction through the TCR, HCP was expressed as a chimeric molecule with extracellular and transmembrane domains of the HLA-A2 molecule (A2/HCP) on wild-type Jurkat T cells and the CD45-deficient variant, J45.01. In this report, we show that expression of A2/HCP, unlike A2 chimeras containing the enzymatic regions of CD45, fails to rescue TCR-mediated signal transduction in J45.01. Furthermore, expression of A2/HCP on wild-type Jurkat T cells results in diminished inositol phosphate production following TCR ligation as well as markedly diminished nuclear factor of activated T cells promoter activity. Surprisingly, however, TCR-mediated tyrosine phosphorylation of phospholipase C gamma 1 remains intact in the Jurkat cells expressing the A2/HCP chimera. These experiments provide further evidence that HCP can serve a negative regulatory role in receptor-mediated signaling in immune cells. Additionally, our studies suggest that surface expression of HCP in T cells may provide a means to identify phosphotyrosine-containing proteins that are required for coupling signaling pathways initiated by ligation of the T cell Ag receptor.
Musci
M A
MA
Graduate Program in Immunology, University of Iowa College of Medicine, Iowa City 52242, USA.
Beaves
S L
SL
Ross
S E
SE
Yi
T
T
Koretzky
G A
GA
D002118:Calcium / Q000378:metabolism; D002999:Clone Cells; D004268:DNA-Binding Proteins / Q000378:metabolism; D004790:Enzyme Induction / Q000276:immunology; D006412:Hematopoietic Stem Cells / Q000201:enzymology* / Q000276:immunology; D006801:Humans; D015544:Inositol 1,4,5-Trisphosphate / Q000096:biosynthesis; D007295:Inositol Phosphates / Q000096:biosynthesis; D047908:Intracellular Signaling Peptides and Proteins; D007527:Isoenzymes / Q000378:metabolism; D019169:Jurkat Cells; D017493:Leukocyte Common Antigens / Q000096:biosynthesis / Q000235:genetics*; D008213:Lymphocyte Activation; D008565:Membrane Proteins / Q000096:biosynthesis* / Q000502:physiology; D050778:NFATC Transcription Factors; D009687:Nuclear Proteins; D051966:Phospholipase C gamma; D010766:Phosphorylation; D053824:Protein Tyrosine Phosphatase, Non-Receptor Type 6; D017027:Protein Tyrosine Phosphatases / Q000096:biosynthesis* / Q000276:immunology / Q000502:physiology*; D011948:Receptors, Antigen, T-Cell / Q000378:metabolism / Q000502:physiology*; D011993:Recombinant Fusion Proteins / Q000096:biosynthesis; D015398:Signal Transduction / Q000276:immunology*; D014157:Transcription Factors / Q000378:metabolism; D010738:Type C Phospholipases / Q000378:metabolism
D004268:DNA-Binding Proteins; D007295:Inositol Phosphates; D047908:Intracellular Signaling Peptides and Proteins; D007527:Isoenzymes; D008565:Membrane Proteins; D050778:NFATC Transcription Factors; D009687:Nuclear Proteins; D011948:Receptors, Antigen, T-Cell; D011993:Recombinant Fusion Proteins; D014157:Transcription Factors; D015544:Inositol 1,4,5-Trisphosphate; D017493:Leukocyte Common Antigens; C509249:PTPN6 protein, human; D053824:Protein Tyrosine Phosphatase, Non-Receptor Type 6; D017027:Protein Tyrosine Phosphatases; D010738:Type C Phospholipases; D051966:Phospholipase C gamma; D002118:Calcium