Requirement of PI3-kinase activity for the nuclear transport of prolactin in cloned murine T lymphocytes

The murine T-cell clone, L2, requires both IL2 and PRL to proliferate. Prol iferation and selected IL2-driven gene expression are blocked by treatment with rapamycin. Since prolactin translocation to the nucleus is IL2 depende nt and required for proliferation, experiments were performed to identify a ctivation pathways that might be involved in nuclear transport and prolifer ation. L2 cells were stimulated with IL2 in the presence and absence of the mTOR inhibitor rapamycin, PI3-kinase inhibitors (wortmannin, LY294002), th e p38 MAP kinase inhibitor SB203580 and the vitamin D analog calcipotriol. The immunosuppressant rapamycin markedly inhibited IL2-induced proliferatio n and prolactin translocation to the nucleus. Similarly, wortmannin and LY2 94002 inhibited IL2-induced proliferation and markedly decreased the amount of prolactin transported to the nucleus. SB203580 and calcipotriol partial ly inhibited IL2-induced proliferation but had no effect on prolactin trans location. None of the inhibitors affected Lucifer Yellow uptake indicating that rapamycin, wortmannin and LY294002 did not inhibit early endosomal for mation but rather worked to inhibit prolactin translocation at a later poin t in the retrograde transport pathway. (C) 1999 Elsevier Science B.V. All r ights reserved.