- 作者: YUAN YAO; QUN ZHOU; SOLVIG G. Ericson
- 作者服務機構: Blood and Marrow Transplant and Hematologic Malignancy Program, Mary Babb Randolph Cancer Center, West Virginia University, Morgantown, W.Va., USA
- 中文摘要: --
- 英文摘要: lL-6 is involved in the control of differentiation of theacute promyelocytic leukemia cell line, HL-60.However,the participation of protein tyrosine phosphatase(PTP) inthe monocytic differentiation activity of lL-6 at low con-centrations has not been well clarified. In the presentstudy, we demonstrate that lL-6(10 ng/ml)alone in-creased cell growth without differentiation. In the pres-ence of vanadate(10 μM),a PTP inhibitor,lL-6 inducedpronounced GO/G1 cell cycle arrest; this effect was asso-ciated with CD14+ monocytic differentiation as well asF-actin filament polymerization. Furthermore, vanadatepotentiated lL-6-signaling pathway by increasing the ty-rosine phosphorylated levels of STAT3 (Tyr705), andLyn. Such induction of Lyn kinase activity resulted fromhypophosphorylated tyrosine (Tyr507)at its negativeregulatory site. Vanadate also cooperated with lL-6 toform a protein complex containing Lyn and an actin-associated protein, AFAP110. A complex between Lynand AFAP110 may serve to regulate F-actin filamentpolymerization. In conclusion,inhibition of PTP by vana-date promotes hematopoietic differentiation activity oflL-6 through modulating multiple signalings, particularlyactin filament polymerization.
- 中文關鍵字: --
- 英文關鍵字: --