title: Free LIF receptor α-chain distal cytoplasmic motifs enhance Jak2-independent STAT3 phosphorylation and induce differentiation in HL-60 cells.
abstract: The leukemia inhibitory factor (LIF) affects multiple types of leukemia cells in vitro through the functional LIF receptor (LIFR), which comprises a complex of the LIFR α-chain (LIFR α) and gp130. As Jak2/STAT3 has been proven to be a significant mediator in the LIF-induced differentiation of promyeloid leukemia cells, we constructed a recombinant vector, pcDNA3.0-CT3 (containing the structurally conserved triple YXXQ motifs of LIFR α, termed LIFR α-CT3), and its specific tyrosine-mutated counterpart, pcDNA3.0-MUT, to determine the sites and examine the corresponding mechanisms involved in STAT3 phosphorylation. We found that the triple YXXQ motifs of LIFR α-CT3 are capable of up-regulating phosphorylated levels of STAT3 in a Jak2-independent manner prior to the induction of myeloid differentiation by LIFR α-CT3 in the human promyeloid cell line HL-60. By specifically blocking Jak2 using the AG-490 inhibitor, we observed that the LIFR α-CT3 group of HL-60 cells still demonstrated up-regulation of phosphorylated STAT3 and this up-regulation could result in the myeloid differentiation of HL-60 cells. These results may shed light on acute promyeloid leukemia therapy in future clinical practice.
authors.affiliation: Department of Embryology and Histology, Second Military Medical University, Shanghai 200433, PR China.
authors.forename: Qing
authors.initials: Q
authors.lastname: Sun
authors.forename: Jing
authors.initials: J
authors.lastname: Wang
authors.forename: Jun
authors.initials: J
authors.lastname: Xiong
authors.forename: Ling
authors.initials: L
authors.lastname: Yang
authors.forename: Houqi
authors.initials: H
authors.lastname: Liu
mesh_terms: D001483:Base Sequence; D002454:Cell Differentiation / Q000502:physiology; D045744:Cell Line, Tumor; D003593:Cytoplasm / Q000378:metabolism; D018922:HL-60 Cells; D006801:Humans; D053614:Janus Kinase 2 / Q000378:metabolism*; D053605:Leukemia Inhibitory Factor / Q000378:metabolism*; D053680:Leukemia Inhibitory Factor Receptor alpha Subunit / Q000235:genetics / Q000378:metabolism*; D015473:Leukemia, Promyelocytic, Acute / Q000235:genetics / Q000378:metabolism / Q000473:pathology; D008969:Molecular Sequence Data; D010766:Phosphorylation; D050796:STAT3 Transcription Factor / Q000378:metabolism*; D014162:Transfection; D015854:Up-Regulation
chemical_list: C507837:LIF protein, human; C507840:LIFR protein, human; D053605:Leukemia Inhibitory Factor; D053680:Leukemia Inhibitory Factor Receptor alpha Subunit; D050796:STAT3 Transcription Factor; C494086:STAT3 protein, human; D053614:Janus Kinase 2