Stabilization of a protein-tyrosine phosphatase mRNA upon mitogenic stimulation of T-lymphocytes

Abstract

The expression of a non-receptor type protein-tyrosine phosphatase (the T-cell phosphatase or PTP-S) which shows homology with basic domains of Fos and Jun, was investigated upon mitogenic stimulation of rat splenic T lymphocytes. As studied by Northern blot analysis of total cellular RNA, mitogenic stimulation of T lymphocytes by concanavalin A resulted in an increase in the level of PTP-S mRNA; there was little or no change in the level of mRNA coding for PTP-1 (which is also a non-receptor type tyrosine phosphatase). Maximum increase of about 3-fold in the level of PTP-S mRNA occurred after 72 h of mitogenic stimulation. Mitogenic stimulation did not increase the level of PTP-S transcripts in the nucleus. The half-life of PTP-S mRNA in unstimulated lymphocytes was about 25 min which increased to 5 h after mitogenic stimulation. An inhibitor of protein synthesis, cycloheximide, increased the level of PTP-S transcripts by 6-fold in control lymphocytes but did not increase the level of PTP-1 transcripts. Treatment with cycloheximide increased the half-life of PTP-S transcripts in resting lymphocytes. The PTP-S gene product was identified as a 42 kDa polypeptide by immunoblotting. The level of PTP-S gene product increased upon mitogenic stimulation of lymphocytes by Con A and reached a maximum after 72 h, as determined by immunoblotting. These results suggest that post-transcriptional regulation of mRNA stability is an important factor in controlling the level of this phosphatase mRNA during mitogenic stimulation of T-lymphocytes.