Cyclophilin A as a downstream effector of PI3K/Akt signalling pathway in multiple myeloma cells

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.

Source: Cell Biochemistry and Function - December 21, 2015 Category: Biochemistry Authors: Zuo‐Lin Lin, Hsin‐Jou Wu, Jin‐An Chen, Kuo‐Chih Lin, Jung‐Hsin Hsu Tags: Research Article Source Type: research