STABILIZATION OF A PROTEIN-TYROSINE-PHOSPHATASE MESSENGER-RNA UPON MITOGENIC STIMULATION OF T-LYMPHOCYTES

The expression of a non-receptor type protein-tyrosine phosphatase (th e T-cell phosphatase or PTP-S) which shows homology with basic domains of Fos and Jun, was investigated upon mitogenic stimulation of rat sp lenic T lymphocytes. As studied by Northern blot analysis of total cel lular RNA, mitogenic stimulation of T lymphocytes by concanavalin A re sulted 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-r eceptor type tyrosine phosphatase). Maximum increase of about 3-fold i n the level of PTP-S mRNA occurred after 72 h of mitogenic stimulation . Mitogenic stimulation did not increase the level of PTP-S transcript s in the nucleus. The half-life of PTP-S mRNA in unstimulated lymphocy tes was about 25 min which increased to 5 h after mitogenic stimulatio n. An inhibitor of protein synthesis, cycloheximide, increased the lev el of PTP-S transcripts by 6-fold in control lymphocytes but did not i ncrease the level of PTP-1 transcripts. Treatment with cycloheximide i ncreased the half-life of PTP-S transcripts in resting lymphocytes. Th e PTP-S gene product was identified as a 42 kDa polypeptide by immunob lotting. The level of PTP-S gene product increased upon mitogenic stim ulation of lymphocytes by Con A and reached a maximum after 72 h, as d etermined by immunoblotting. These results suggest that post-transcrip tional regulation of mRNA stability is an important factor in controll ing the level of this phosphatase mRNA during mitogenic stimulation of T-lymphocytes.