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Insulin‐like growth factor‐1 activates Akt and Jun N‐terminal kinases (JNKs) in promoting the survival of T lymphocytes
Author(s) -
Walsh Patrick T.,
Smith Loraine M.,
O'Connor Rosemary
Publication year - 2002
Publication title -
immunology
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 2.297
H-Index - 133
eISSN - 1365-2567
pISSN - 0019-2805
DOI - 10.1046/j.1365-2567.2002.01525.x
Subject(s) - jurkat cells , phosphorylation , protein kinase b , microbiology and biotechnology , transfection , kinase , cd28 , biology , ly294002 , growth factor , t cell , cell culture , receptor , immunology , biochemistry , immune system , genetics
Summary Insulin‐like growth factor 1 receptor (IGF‐1R) expression is augmented on T cells upon ligation of CD28, and this promotes IGF‐1‐mediated protection from Fas‐induced cell death for up to 6 days. To determine the mechanism of action of IGF‐1R in T‐cell expansion, we investigated the signalling pathways activated by IGF‐1 in T cells and in Jurkat cells. We found that IGF‐1 transiently induces Akt, jun N‐terminal kinases (JNK), and c‐Jun phosphorylation in activated T cells, with JNK and c‐Jun phosphorylation occurring faster than Akt phosphorylation. To mimic IGF‐1R expression levels in CD28‐stimulated Jurkat cells these cells were stably transfected to over‐express the IGF‐1R. Jurkat/IGF‐1R cells exhibited enhanced constitutive Akt phosphorylation compared with mock‐transfected controls, but IGF‐1 induced transient phosphorylation of MKK4, JNKs, and c‐Jun. Inhibition of PI‐3 kinase activity and Akt phosphorylation with LY294002 totally suppressed IGF‐1‐mediated protection from Fas killing in activated T cells, but only partially suppressed IGF‐1‐mediated protection in Jurkat/IGF‐1R cells. However, either dicumarol in T cells or a dominant negative JNK1 (APF) in Jurkat/IGF‐1R cells greatly suppressed IGF‐1‐mediated protection from Fas killing. Together, these data demonstrate that IGF‐1‐mediated activation of JNKs and PI‐3 kinase contributes to normal T‐cell survival, whereas the JNK pathway may be more important in Jurkat leukaemia cells.