Gene/Protein Disease Symptom Drug Enzyme Compound
Pivot Concepts:   Target Concepts:
Query: UNIPROT:P10721 (c-kit)
 6,575 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

Cell migration is one of the fundamental cellular responses governing development, homeostasis and disorders of the body. Therefore, artificial control of cell migration holds great promise for the treatment of many diseases. In this study, we developed an artificial cell migration system based on chimeric receptors that can respond to an artificial ligand that is quite different from natural chemoattractants. Chimeric receptors consisting of an anti-fluorescein single-chain Fv tethered to the extracellular D2 domain of erythropoietin receptor (EpoR) and the transmembrane/cytoplasmic domains of EpoR, gp130, interleukin-2 receptor, c-Kit, c-Fms, epidermal growth factor receptor (EGFR) or insulin receptor were expressed in the murine Ba/F3 pro-B cell line. Migration assays revealed that chimeric receptors containing the cytoplasmic domain of c-Kit, c-Fms or EGFR transduced migration signals in response to fluorescein-conjugated bovine serum albumin (BSA-FL). Furthermore, based on the cell migration in response to BSA-FL, we successfully selected genetically modified cells from mixtures of gene-transduced and untransduced cells. This study represents the first demonstration of cell migration in response to an artificial ligand that is quite different from natural chemoattractants, suggesting its potential application to immunotherapies and tissue engineering.
 ...
PMID:Antigen-mediated migration of murine pro-B Ba/F3 cells via an antibody/receptor chimera. 1796 83

Interleukin (IL)-27, one of the most recently discovered IL-6 family cytokines, activates both the signal transducer and activator of transcription (STAT)1 and STAT3, and plays multiple roles in pro- and anti-inflammatory immune responses. IL-27 acts on various types of cells including T, B, and macrophage through the common signal-transducing receptor gp130 and its specific receptor WSX-1, but the effect of IL-27 on hematopoietic stem cells (HSCs) remains unknown. Here, we show that IL-27 together with stem cell factor (SCF) directly acts on HSCs and supports their early differentiation in vitro and in vivo. CD34(-/low)c-Kit(+)Sca-1(+)lineage marker(-) (CD34(-)KSL) cells, a population highly enriched in mouse HSCs, were found to express both IL-27 receptor subunits. In vitro cultures of CD34(-)KSL cells with IL-27 and SCF resulted in an expansion of progenitors including short-term repopulating cells, while some of their long-term repopulating activity also was maintained. To examine its in vivo effect, transgenic mice expressing IL-27 were generated. These mice exhibited enhanced myelopoiesis and impaired B lymphopoiesis in the bone marrow with extramedullary hematopoiesis in the spleen. Moreover, IL-27 similarly acted on human CD34(+) cells. These results suggest that IL-27 is one of the limited cytokines that play a role in HSC regulation.
 ...
PMID:Interleukin-27 directly induces differentiation in hematopoietic stem cells. 1804 4

The molecular mechanisms regulating the expansion of the hematopoietic system including hematopoietic stem cells (HSCs) in the fetal liver during embryonic development are largely unknown. The LIM-homeobox gene Lhx2 is a candidate regulator of fetal hematopoiesis since it is expressed in the fetal liver and Lhx2(-/-) mice die in utero due to severe anemia. Moreover, expression of Lhx2 in embryonic stem (ES) cell-derived embryoid bodies (EBs) can lead to the generation of HSC-like cell lines. To further define the role of this transcription factor in hematopoietic regulation, we generated ES cell lines that enabled tet-inducible expression of Lhx2. Using this approach we observed that Lhx2 expression synergises with specific signalling pathways, resulting in increased frequency of colony forming cells in developing EB cells. The increase in growth factor-responsive progenitor cells directly correlates to the efficiency in generating HSC-like cell lines, suggesting that Lhx2 expression induce self-renewal of a distinct multipotential hematopoietic progenitor cell in EBs. Signalling via the c-kit tyrosine kinase receptor and the gp130 signal transducer by IL-6 is necessary and sufficient for the Lhx2 induced self-renewal. While inducing self-renewal of multipotential progenitor cells, expression of Lhx2 inhibited proliferation of primitive erythroid precursor cells and interfered with early ES cell commitment, indicating striking lineage specificity of this effect.
 ...
PMID:Lhx2 expression promotes self-renewal of a distinct multipotential hematopoietic progenitor cell in embryonic stem cell-derived embryoid bodies. 1843 2

IL-27 was first discovered as a factor supporting initial Th1 immune responses. Subsequent studies revealed that this cytokine has pleiotropic effects, including inhibition of certain immune cells, a regulatory role in hemopoietic stem cell differentiation, and antitumor activities. However, the role of human IL (hIL)-27 in human osteoclast precursors and inflammatory bone disease is unclear. Here, we examined the direct effect of hIL-27 on human osteoclastogenesis. Human bone marrow cells cultured in MethoCult medium containing human (h) GM-CSF, human stem cell factor, and hIL-3 expressed Mac-1, c-kit, and c-Fms. These cells, called hCFU-GMs, also expressed the IL-27 receptor, an IL-27Ralpha (WSX-1)/gp130 heterodimer. Cultivation in hM-CSF and human receptor activator of NF-kappaB ligand induced the differentiation of tartrate-resistant acid phosphatase-positive multinucleated cells (osteoclasts) from hCFU-GMs, and hIL-27 inhibited this osteoclastogenesis in a dose-dependent manner. hIL-27 also repressed bone resorption by osteoclasts on a dentine slice. hIL-27 caused a remarkable increase in STAT1 phosphorylation and enhanced the STAT1 protein level. It also inhibited the expression of receptor activator of NF-kappaB ligand-induced c-Fos and cytoplasmic, calcineurin-dependent 1 NFAT (NFATc1), which are indispensable transcription factors for osteoclastogenesis. Fludarabine, a STAT1 inhibitor, and STAT1 small interfering RNA partially rescued the inhibition of osteoclastogenesis by IL-27. A WSX-1 deficiency caused severe inflammatory bone destruction primed by Escherichia coli cell wall lysate in vivo. Therefore, hIL-27 may act as an anti-inflammatory cytokine in human bone destruction, by inhibiting osteoclastogenesis from hCFU-GMs via STAT1-dependent down-regulation of the transcription factor c-Fos. Our results suggest that hIL-27 may prove useful as a therapeutic target for inflammatory bone destruction.
 ...
PMID:IL-27 abrogates receptor activator of NF-kappa B ligand-mediated osteoclastogenesis of human granulocyte-macrophage colony-forming unit cells through STAT1-dependent inhibition of c-Fos. 1962 Mar 1

A complex of soluble interleukin-6 receptor (sIL-6R) and interleukin-6 has been shown to play some roles in human hematopoiesis. It activates gp130 signal to stimulate human erythroid, megakaryocytic and primitive hematopoietic progenitor cells, which express gp130 but not IL-6R, in the presence of c-Kit signal mediated by stem cell factor (SCF). The culture system using a combination of sIL-6R, IL-6 and SCF can be useful for ex vivo expansion of human hematopoietic stem/progenitor cells and provide a novel way for gene transfer into human hematopoietic stem cells.
...
PMID:Role of Soluble Interleukin-6 Receptor With Interleukin-6 in Human Hematopoiesis. 2740 5


<< Previous 1 2 3