Protein tyrosine kinase activity in T lymphocytes from patients with systemic lupus erythematosus.
We have recently observed an abnormal pattern of protein tyrosine phosphoryl-ation in resting T lymphocytes obtained from peripheral blood of patients with systemic lupus erythematosus (SLE). To examine whether these findings may be related to dysregulated protein tyrosine kinase (PTK) function, we tested the relative amount and enzyme activity of the main PTKs involved in the earliest signalling steps triggered via the CD3 pathway. Cell lysates from peripheral blood T cells in SLE patients showed lower amounts of p59(fyn) and p56(lck) as shown by immunoblot. In contrast, the amount of ZAP-70, a PTK of the syk family, was comparable in both groups. However, p59(fyn) immuno-precipitates obtained from unstimulated peripheral blood SLE T cells showed enhanced PTK activity as compared to controls, whereas the PTK activity of p56(lck) and ZAP-70 molecules was comparable in both groups. The unchecked activity of the TCR/CD3-associated src kinase p59(fyn) may alter the balance needed for regulated T cell responses in SLE patients.
Blasini
A M
AM
Centro Nacional de Enfermedades Reumáticas, Hospital Universitario de Caracas, Caracas, Venezuela.
Brundula
V
V
Paris
M
M
Rivas
L
L
Salazar
S
S
Stekman
I L
IL
Rodriguez
M A
MA
D000328:Adult; D017252:CD3 Complex / Q000378:metabolism; D016022:Case-Control Studies; D005260:Female; D006801:Humans; D008180:Lupus Erythematosus, Systemic / Q000201:enzymology* / Q000276:immunology; D008213:Lymphocyte Activation; D019860:Lymphocyte Specific Protein Tyrosine Kinase p56(lck) / Q000097:blood; D008297:Male; D011505:Protein-Tyrosine Kinases / Q000097:blood*; D011518:Proto-Oncogene Proteins / Q000097:blood; D051076:Proto-Oncogene Proteins c-fyn; D011948:Receptors, Antigen, T-Cell / Q000378:metabolism; D015398:Signal Transduction; D013601:T-Lymphocytes / Q000201:enzymology* / Q000276:immunology; D051746:ZAP-70 Protein-Tyrosine Kinase
D017252:CD3 Complex; D011518:Proto-Oncogene Proteins; D011948:Receptors, Antigen, T-Cell; D011505:Protein-Tyrosine Kinases; C494957:FYN protein, human; D019860:Lymphocyte Specific Protein Tyrosine Kinase p56(lck); D051076:Proto-Oncogene Proteins c-fyn; D051746:ZAP-70 Protein-Tyrosine Kinase; C497261:ZAP70 protein, human