Premium
Cyclophilin A as a downstream effector of PI3K/Akt signalling pathway in multiple myeloma cells
Author(s) -
Lin ZuoLin,
Wu HsinJou,
Chen JinAn,
Lin KuoChih,
Hsu JungHsin
Publication year - 2015
Publication title -
cell biochemistry and function
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 0.933
H-Index - 61
eISSN - 1099-0844
pISSN - 0263-6484
DOI - 10.1002/cbf.3156
Subject(s) - protein kinase b , phosphorylation , pi3k/akt/mtor pathway , microbiology and biotechnology , cyclophilin a , effector , biology , stat3 , kinase , signal transduction , chemistry , cancer research
Cyclophilin A (Cyp A), a member of the peptidyl‐prolyl isomerase (PPI) family, may function as a molecular signalling switch. Comparative proteomic studies have identified Cyp A as a potential downstream target of protein kinase B (Akt). This study confirmed that Cyp A is a downstream effector of the phosphatidylinositide 3‐kinase (PI3K)/Akt signalling pathway. Cyp A was highly phosphorylated in response to interleukin‐6 treatment, which was consistent with the accumulation of phosphorylated Akt, suggesting that Cyp A is a phosphorylation target of Akt and downstream effector of the PI3K/Akt pathway. Cyclosporine A (CsA), a PPI inhibitor, inhibited the growth of multiple myeloma (MM) U266 cells. Moreover, CsA treatment inhibited the activation of the signal transducer and activator of transcription 3 (STAT3) in MM U266 cells. Several Cyp A mutants were generated. Mutants with mutated AKT phosphorylation sites increased the G1 phase arrest in MM U266 cells. The other mutants that mimicked the phosphorylated state of Cyp A decreased the percentage of G1 phase. These results demonstrated that the states of phosphorylation of Cyp A by Akt can influence the progress of the cell cycle in MM U266 cells and that this effect is probably mediated through the Janus‐activated kinase 2/STAT3 signalling pathway. Copyright © 2015 John Wiley & Sons, Ltd.