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 phosphatase (PTP) in autoimmune MRL/MpJ-lpr/lpr mice (lpr mice) were measured and compared with the activities in the tissues from MRL/MpJ-+/+ mice (+/+ mice) as the control, In the spleen and liver, PTK activities in cytosol and membrane fractions were about 1.7- and 1.3-fold, respectively, higher in lpr mice than +/+ mice, PTP activities in cytosol and membrane fractions from Ipr mice were 1.7- and 1.3-fold, respectively, higher in spleen, and 2.5- and 1.3-fold, respectively, higher in liver compared with those of the controls, These results demonstrate that the mutation of Ipr gene resulted in elevation of PTK and PTP activities, Then, we measured the amounts and activities of SH-PTP1, a cytosolic PTP playing a crucial role in intracellular signaling from Fas antigen. The amounts of SH-PTP1 were about 4-fold larger in thymus, spleen, and lymphnodes than in liver, but there was no marked difference in the amounts between Ipr and +/+ mice, On the other hand, activity of SH-PTP1 was definitely lower in Ipr spleen and lymphnodes than +/+ spleen, but several times higher in Ipr liver than +/+ liver, Tyrosine phosphorylation levels of SH-PTP1 in spleen of Ipr and +/+ mice were similar, 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.