TY - JOUR
T1 - Requirement of PI3-kinase activity for the nuclear transport of prolactin in cloned murine T lymphocytes
AU - Belkowski, Stanley M.
AU - Levine, Jason E.
AU - Prystowsky, Michael B.
N1 - Copyright:
Copyright 2007 Elsevier B.V., All rights reserved.
PY - 1999/2/1
Y1 - 1999/2/1
N2 - The murine T-cell clone, L2, requires both IL2 and PRL to proliferate. Proliferation and selected IL2-driven gene expression are blocked by treatment with rapamycin. Since prolactin translocation to the nucleus is IL2 dependent and required for proliferation, experiments were performed to identify activation pathways that might be involved in nuclear transport and proliferation. L2 cells were stimulated with IL2 in the presence and absence of the mTOR inhibitor rapamycin, PI3-kinase inhibitors (wortmannin. LY294002), the p38 MAP kinase inhibitor SB203580 and the vitamin D analog calcipotriol. The immunosuppressant rapamycin markedly inhibited IL2-induced proliferation and prolactin translocation to the nucleus. Similarly, wortmannin and LY294002 inhibited IL2-induced proliferation and markedly decreased the amount of prolactin transported to the nucleus. SB203580 and calcipotriol partially inhibited IL2-induced proliferation but had no effect on prolactin translocation. None of the inhibitors affected Lucifer Yellow uptake indicating that rapamycin, wortmannin and LY294002 did not inhibit early endosomal formation but rather worked to inhibit prolactin translocation at a later point in the retrograde transport pathway.
AB - The murine T-cell clone, L2, requires both IL2 and PRL to proliferate. Proliferation and selected IL2-driven gene expression are blocked by treatment with rapamycin. Since prolactin translocation to the nucleus is IL2 dependent and required for proliferation, experiments were performed to identify activation pathways that might be involved in nuclear transport and proliferation. L2 cells were stimulated with IL2 in the presence and absence of the mTOR inhibitor rapamycin, PI3-kinase inhibitors (wortmannin. LY294002), the p38 MAP kinase inhibitor SB203580 and the vitamin D analog calcipotriol. The immunosuppressant rapamycin markedly inhibited IL2-induced proliferation and prolactin translocation to the nucleus. Similarly, wortmannin and LY294002 inhibited IL2-induced proliferation and markedly decreased the amount of prolactin transported to the nucleus. SB203580 and calcipotriol partially inhibited IL2-induced proliferation but had no effect on prolactin translocation. None of the inhibitors affected Lucifer Yellow uptake indicating that rapamycin, wortmannin and LY294002 did not inhibit early endosomal formation but rather worked to inhibit prolactin translocation at a later point in the retrograde transport pathway.
KW - PI3-kinase
KW - Prolactin
KW - Rapamycin
KW - T-cell activation
KW - Wortmannin
UR - http://www.scopus.com/inward/record.url?scp=0033081686&partnerID=8YFLogxK
UR - http://www.scopus.com/inward/citedby.url?scp=0033081686&partnerID=8YFLogxK
U2 - 10.1016/S0165-5728(98)00202-1
DO - 10.1016/S0165-5728(98)00202-1
M3 - Article
C2 - 10376934
AN - SCOPUS:0033081686
SN - 0165-5728
VL - 94
SP - 40
EP - 47
JO - Journal of Neuroimmunology
JF - Journal of Neuroimmunology
IS - 1-2
ER -