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

In this report we evaluated the exact expression pattern of c-Kit on mobilized peripheral blood (PB) CD34+ cells. Using a monoclonal antibody against CD117 antigen (95C3), flow cytometric analysis revealed that approximately 25% of the mobilized PB CD34+ cells coexpress c-Kit. This cell fraction showed a considerable heterogeneity with respect to c-Kit expression, consisting of a small fraction with high levels of c-Kit (4.2%) (CD34+/CD117high fraction) and a larger proportion of cells expressing low levels of this antigen (21.0%) (CD34+/CD117low fraction). Clonogenic assays showed that CD34+/CD117high cell fraction consisted almost exclusively of erythroid progenitors, in contrast to CD34+/CD117low cell subset which gave rise mostly to granulocyte-monocyte colonies. The majority of CFU-GEMM and the most primitive week 6 cobblestone area forming cells (CAFCs) segregated in the CD34+/CD117low cell subset, suggesting the highest content of multipotential progenitors within this cell fraction. None of the sorted cell subsets was able to produce reactive oxygen intermediates (ROI). However, ex vivo expansion of the sorted subsets with interleukin 3, stem cell factor and FLT3 ligand for 2 weeks resulted in a significant production of O2- and H2O2/HOCl by CD34+/CD117low cell fraction, compared to the same sorted but not expanded counterparts. According to the major content of multipotential hematopoietic progenitors and highest capacity to generate sufficient amounts of ROI after ex vivo expansion, we suggest that CD34+/CD117low cell subset would be one of the most potential candidates for transplantation in patients with acute lymphoblastic leukemia, which lack c-Kit antigen expression.
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PMID:Phenotypic and functional characterization of mobilized peripheral blood CD34+ cells coexpressing different levels of c-Kit. 966 40

This work aims to elucidate the mechanisms involved in the early activation of glucose transport in hematopoietic M07e cells by stem cell factor (SCF) and a reactive oxygen species (ROS) as H2O2. SCF and H2O2 increase Vmax for glucose transport; this enhancement is due to a higher content in GLUT1 in plasma membranes, possibly through a translocation from intracellular stores. Inhibitors of tyrosine kinases or phospholipase C (PLC) remove glucose transport enhancement and prevent translocation. The inhibitory effect of STI-571 suggests a role for c-kit tyrosine kinase on glucose transport activation not only by SCF, but also by H2O2. On the other hand, neither protein kinase C nor phosphoinositide-3-kinase appear to be involved in the acute activation of glucose transport. Our data suggest that i) in M07e cells, SCF and exogenous H2O2 elicit a short-term activation of glucose transport through a translocation of GLUT1 from intracellular stores to plasma membranes; ii) both stimuli could share at least some signaling pathways leading to glucose uptake activation, involving protein tyrosine kinases and PLC iii) H2O2 could act increasing the level of tyrosine phosphorylation through the inhibition of tyrosine phosphatases and mimicking the regulation role of endogenous ROS.
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PMID:Stem cell factor and H2O2 induce GLUT1 translocation in M07e cells. 1532 33

In leukemic cells, glucose transport is activated by SCF and H2O2 through a common signal cascade involving Akt, PLCgamma, Syk, and the Src family, in this order. An explanation can be provided by the phosphorylation of c-kit, the SCF receptor, elicited by either SCF or H2O2. Moreover, antioxidants prevent the SCF effect on glucose transport, confirming the involvement of H2O2 in the pathway leading to glucose-transport activation and suggesting a potential role for reactive oxygen species in leukemia proliferation.
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PMID:Glucose-transport regulation in leukemic cells: how can H2O2 mimic stem cell factor effects? 1711 33