| Leukemia inhibory factor (LIF), a member of the family of multifunctional cytokines, can inhibit the proliferation of leukemia cells, such as HL-60, U937 and Ml. The characteristic with fast growth and with bad ability to the reaction of LIF of the leukemia cell, Make limited LIF can't be suppressed the malignant hyperplasia of the leukemia cell human body. LIF of the foreign aid nature and not the physiology dosage have toxicity for normal cells. So the medical value of LIF can't get applicationLIF exerts its biological activities through a specific cell-surface receptor (LIFR), LIF receptor is multimeric shares a a subunit, the low-affinity LIF receptor (gpl90), and an additional subunit, IL-6 related signal transducer (gpl30). Human LIFR is an approximately 110-kDa protein that is glycosylated to about 190 kDa at multiple potential N-linked glycosylation sites. Human LIFRoc preprotein is 1097 aa, encompassing a signal sequence of 44 aa, an extracellular domain of 789 aa, a transmembrane domain of 26 aa, and a cytoplasmic domain of 23 8 aa. Human gp 130 and gpl90 have in the cytoplasmic domains 277 and 238 amino acid residues, respectively, and lack intrinsic kinase activity. The first 60 residues of the cytoplasmic domains of gp 130 are sufficient to mediate a proliferation signal, and contain two conserved motifs (termed Box 1 and Box2) that are critical for Jakl, Jak2 and Tyk2 activation. The first 150 amino acid residues of the LIFRa cytoplasmic domain are found to be necessary for signaling of IL-6 responsive gene elements, as well as a functionally critical sequence between residues 141-150 is also necessary for both gpl30 and G-CSFR. gpl90 contains the extracellular region and transmembrane region and the cytoplasmic region. The cytoplasmic domains of gp190 contain three conserved motifs, contained contains an YXXQ consensus sequence. LIF receptor initiates signaling by inducing heterodimerization of gp130 with LIF receptor a component (LIFRa). In the beginning, Studies revealed thatLIFRa that binds LIF with low affinity and gp130 that can convert a low affinity receptor complex to a high affinity receptor complex. Cytokines and growth factors interact with the cell surface receptors to activate the downstream signaling pathway, lead to intracellular signaling. These pathways transduce specific responses to the nucleus, culminating in induction of transcription of discrete sets of target genes. A number of groups have investigated the specific contributions of the LIFRa and gp130 cytoplasmic domain to LIF induced signal transduction using a variety of cell lines, for instance, Cos7 cells, the murine myeloid leukemia cell line Ml, 3T3-L1 cells, human and rat hepatoma cells, and Ba/F3 cells. However, there are controversial data in the literature apparently due to the use of different cell lines. There are differences in signaling capacity or expression of signaling proteins for each kind of cell line.Intracellular signaling pathways of LIF concern the activation of both Tyr and Ser/Thr protein kinases and two signal-transducing pathways, the Janus kinase signal transducer and activator of transcription (JAK-STAT) pathway and the Ras-mitogen-activated protein kinase (MAPK) pathway. The two signal-transducing pathways have been recognized in leukemia cells. The separate contributions of the cytoplasmic domain of LIFRa and gp130 to ligand-induced signal transductions have been investigated in some different cells. However, the results demonstrate that the singnaling potential of LIFRa and gp130 varies in differences in the signaling molecules activated according to the state and living surrounding of the cells. Stat3 is specifically tyrosine-phosphorylated and activated by stimulation with cytokines in various cell types. Stat3 activation is the critical step in a cascade of events that leads to terminal differentiation of Ml cells. Otherwise, Stat3 mediates the rapid activation of the c-myc gene upon stimulation of gp130 through its binding to a region overlapping with the E2F site within the c-myc prom...
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