In:
Cell Biochemistry and Function, Wiley, Vol. 33, No. 8 ( 2015-12), p. 566-574
Kurzfassung:
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.
Materialart:
Online-Ressource
ISSN:
0263-6484
,
1099-0844
Sprache:
Englisch
Verlag:
Wiley
Publikationsdatum:
2015
ZDB Id:
1496553-7
SSG:
12
