Vanadate stimulates monocytic differentiation activity of IL-6 by enhancing actin filament polymerization in HL-60 cells.
IL-6 is involved in the control of differentiation of the acute promyelocytic leukemia cell line, HL-60. However, the participation of protein tyrosine phosphatase (PTP) in the monocytic differentiation activity of IL-6 at low concentrations has not been well clarified. In the present study, we demonstrate that IL-6 (10 ng/ml) alone increased cell growth without differentiation. In the presence of vanadate (10 microM), a PTP inhibitor, IL-6 induced pronounced G0/G1 cell cycle arrest; this effect was associated with CD14+ monocytic differentiation as well as F-actin filament polymerization. Furthermore, vanadate potentiated IL-6-signaling pathway by increasing the tyrosine phosphorylated levels of STAT3 (Tyr705), and Lyn. Such induction of Lyn kinase activity resulted from hypophosphorylated tyrosine (Tyr507) at its negative regulatory site. Vanadate also cooperated with IL-6 to form a protein complex containing Lyn and an actin-associated protein, AFAP110. A complex between Lyn and AFAP110 may serve to regulate F-actin filament polymerization. In conclusion, inhibition of PTP by vanadate promotes hematopoietic differentiation activity of IL-6 through modulating multiple signalings, particularly actin filament polymerization.
Yao
Yuan
Y
Blood and Marrow Transplant and Hematologic Malignancy Program, Mary Babb Randolph Cancer Center, West Virginia University, Morgantown, W.Va. 26506, USA.
Zhou
Qun
Q
Ericson
Solveig G
SG
D000199:Actins / Q000378:metabolism*; D015153:Blotting, Western; D002453:Cell Cycle; D002454:Cell Differentiation; D049109:Cell Proliferation; D005434:Flow Cytometry; D018922:HL-60 Cells; D006801:Humans; D047468:Immunoprecipitation; D015850:Interleukin-6 / Q000378:metabolism*; D008856:Microscopy, Fluorescence; D009000:Monocytes / Q000166:cytology* / Q000187:drug effects / Q000473:pathology; D010766:Phosphorylation; D017027:Protein Tyrosine Phosphatases / Q000378:metabolism; D014638:Vanadates / Q000494:pharmacology*; D019061:src-Family Kinases / Q000378:metabolism
D000199:Actins; D015850:Interleukin-6; D014638:Vanadates; C060902:lyn protein-tyrosine kinase; D019061:src-Family Kinases; D017027:Protein Tyrosine Phosphatases