ALTERATIONS IN ACTIVITY OF PROTEIN-TYROSINE-PHOSPHATASE SH-PTP1 IN AUTOIMMUNE MRL MPJ-LPR/LPR MICE/

Activities of protein tyrosine kinase (PTK) and protein tyrosine phosp hatase (PTP) in autoimmune MRL/MpJ-lpr/lpr mice (lpr mice) were measur ed and compared with the activities in the tissues from MRL/MpJ-+/+ mi ce (+/+ mice) as the control, In the spleen and liver, PTK activities in cytosol and membrane fractions were about 1.7- and 1.3-fold, respec tively, higher in lpr mice than +/+ mice, PTP activities in cytosol an d membrane fractions from Ipr mice were 1.7- and 1.3-fold, respectivel y, higher in spleen, and 2.5- and 1.3-fold, respectively, higher in li ver compared with those of the controls, These results demonstrate tha t the mutation of Ipr gene resulted in elevation of PTK and PTP activi ties, Then, we measured the amounts and activities of SH-PTP1, a cytos olic PTP playing a crucial role in intracellular signaling from Fas an tigen. The amounts of SH-PTP1 were about 4-fold larger in thymus, sple en, and lymphnodes than in liver, but there was no marked difference i n the amounts between Ipr and +/+ mice, On the other hand, activity of SH-PTP1 was definitely lower in Ipr spleen and lymphnodes than +/+ sp leen, but several times higher in Ipr liver than +/+ liver, Tyrosine p hosphorylation levels of SH-PTP1 in spleen of Ipr and +/+ mice were si milar, However, in liver, it was less phosphorylated in Ipr than in +/ + mice, This hypophosphorylation might cause the activation of SH-PTP1 activity in Ipr liver.