Lysophospholipids synergistically promote primitive hematopoietic cell chemotaxis via a mechanism involving Vav 1

Whetton, Anthony D.; Lu, Yuning; Pierce, Andrew; Carney, Louise; Spooncer, Elaine

doi:10.1182/blood-2002-12-3635

Cited by 64 publications

(68 citation statements)

References 32 publications

(28 reference statements)

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“…In other studies including our own, toxin B was found to reduce the migratory response of HPC to SDF1a, to the lysophospholipids sphingosine-1-phosphate and lysophosphatidic acid [27], or short-term bone marrow homing in mice [7,28]. The altered migration behavior of HPC treated with the Rho inhibitor C2I-C3 was opposite to their response to LT or toxin B, which both affect Rac: C2I-C3 resulted in increased migration speed whereas LT and toxin B decreased the migration speed.…”

Section: Effects Of Gtpase Modification On Migration and Hematopoietisupporting

confidence: 51%

Role of the monomeric GTPase Rho in hematopoietic progenitor cell migration and transplantation

et al. 2005

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To investigate the role of the monomeric guanosine triphosphatase (GTPase) Rho on migration of hematopoietic progenitor cells (HPC), we employed different clostridial toxins which inhibit the Rho family of GTPases. Pretreatment with C2I‐C3, a cell‐accessible C3 transferase fusion protein that targets Rho, increased chemokinetic migration of the factor‐dependent multipotent cell line Factor Dependent Cell Paterson with mixed lineage differentiation potential (FDCP‐mix) and of primary lineage marker‐depleted HPC in vitro. In contrast, treatment with lethal toxin (LT) from Clostridium sordellii, which predominantly inactivates Rac, and with toxin B from C. difficile, which inactivates Rho, Rac and Cdc42, decreased in vitro migration. When HPC pretreated with LT or toxin B were transplanted into mice, homing to the bone marrow was impaired, whereas C2I‐C3 treatment did not alter HPC homing. However, in a competitive hematopoietic repopulation experiment in C57BL/6 mice, pretreatment of bone marrow cells with any of the inhibitors, including the Rho inhibitor C2I‐C3, resulted in suppressed donor‐type hematopoiesis. Our data indicate that whereas Rac supports HPC cell cycling, migration, short‐term homing and hematopoietic regeneration, Rho coordinates down‐regulation of HPC migration and is required for hematopoietic regeneration.

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Section: Effects Of Gtpase Modification On Migration and Hematopoietisupporting

confidence: 51%

Role of the monomeric GTPase Rho in hematopoietic progenitor cell migration and transplantation

et al. 2005

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“…In mouse hematopoietic progenitors, LPA 1 , LPA 2 , and S1P 1-4 , but not LPA 3 or S1P 5 , were expressed in primitive Lin-Sca þ Kit þ cells isolated from bone marrow. In addition, LPA and S1P enhanced the chemotactic response in primitive HSCs stimulated by stromal-derived factor-1 [21]. However, in human hematopoietic progenitor cells, Human HSCs were seeded in the Methylcellulose-based media with (or without) addition of cytokines (50 ng/ml stem cell factor and 6 IU/ml erythropoietin) and LPA (5 lM).…”

Section: Discussionmentioning

confidence: 99%

Lysophosphatidic Acid Induces Erythropoiesis through Activating Lysophosphatidic Acid Receptor 3

et al. 2011

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Lysophosphatidic acid (LPA), an extracellular lipid mediator, exerts multiple bioactivities through activating G protein-coupled receptors. LPA receptor 3 (LPA 3 ) is a member of the endothelial differentiation gene family, which regulates differentiation and development of the circulation system. However, the relationship among the LPA receptors (LPARs) and erythropoiesis is still not clear. In this study, we found that erythroblasts expressed both LPA 1 and LPA 3 , and erythropoietic defects were observed in zLPA 3 antisense morpholino oligonucleotide-injected zebrafish embryos. In human model, our results showed that LPA enhanced the erythropoiesis in the cord blood-derived human hematopoietic stem cells (hHSCs) with erythropoietin (EPO) addition in the plasma-free culture. When hHSCs were treated with Ki16425, an antagonist of LPA 1 and LPA 3 , erythropoietic process of hHSCs was also blocked, as detected by mRNA and protein expressions of CD71 and GlyA. In the knockdown study, we further demonstrated that specific knockdown of LPA 3 , not LPA 1 , blocked the erythropoiesis. The translocation of b-catenin into the nucleus, a downstream response of LPAR activation, was blocked by Ki16425 treatment. In addition, upregulation of erythropoiesis by LPA was also blocked by quercetin, an inhibitor of the b-catenin/ T-cell factor pathway. Furthermore, the enhancement of LPA on erythropoiesis was diminished by blocking c-Junactivated kinase/signal transducer and activator of transcription and phosphatidylinositol 3-kinase/AKT activation, the downstream signaling pathways of EPO receptor, suggested that LPA might play a synergistic role with EPO to regulate erythropoietic process. In conclusion, we first reported that LPA participates in EPO-dependent erythropoiesis through activating LPA 3 .

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“…⌬⌬Ct values were calculated for each sample against the average of the two housekeeping genes that were used to calculate -fold change using the 2 Ϫ⌬⌬Ct method (20). Chemotaxis Assays-Chemotaxis assays were performed as described previously (21) except that serum-free StemSpan medium (Stem Cell Technologies, Vancouver, British Columbia, Canada) was used to preclude oncogene-mediated responses to serum-associated agonists, and assays were carried out in 24 Transwell plates with 5-m inserts (Sigma).…”

Section: Cell Lines-ba/f3 Cells Were Transfected With Either An Emptymentioning

confidence: 99%

Eight-channel iTRAQ Enables Comparison of the Activity of Six Leukemogenic Tyrosine Kinases

Pierce

Unwin

Evans

et al. 2008

Molecular & Cellular Proteomics

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There are a number of leukemogenic protein-tyrosine kinases (PTKs) associated with leukemic transformation. Although each is linked with a specific disease their functional activity poses the question whether they have a degree of commonality in their effects upon target cells. Exon array analysis of the effects of six leukemogenic PTKs (BCR/ABL, TEL/PDGFR␤, FIP1/PDGFR␣, D816V KIT, NPM/ALK, and FLT3ITD) revealed few common effects on the transcriptome. It is apparent, however, that proteome changes are not directly governed by transcriptome changes. Therefore, we assessed and used a new generation of iTRAQ tagging, enabling eight-channel relative quantification discovery proteomics, to analyze the effects of these six leukemogenic PTKs. Again these were found to have disparate effects on the proteome with few common targets. BCR/ABL had the greatest effect on the proteome and had more effects in common with FIP1/PDGFR␣. The proteomic effects of the four type III receptor kinases were relatively remotely related. The only protein commonly affected was eosinophil-associated ribonuclease 7. Five of six PTKs affected the motility-related proteins CAPG and vimentin, although this did not correspond to changes in motility. However, correlation of the proteomics data with that from the exon microarray not only showed poor levels of correlation between transcript and protein levels but also revealed alternative patterns of regulation of the CAPG protein by different oncogenes, illustrating the utility of such a combined approach. Molecular & Cellular Proteomics 7: 853-863, 2008.

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Lysophospholipids synergistically promote primitive hematopoietic cell chemotaxis via a mechanism involving Vav 1

Cited by 64 publications

References 32 publications

Role of the monomeric GTPase Rho in hematopoietic progenitor cell migration and transplantation

Role of the monomeric GTPase Rho in hematopoietic progenitor cell migration and transplantation

Lysophosphatidic Acid Induces Erythropoiesis through Activating Lysophosphatidic Acid Receptor 3

Eight-channel iTRAQ Enables Comparison of the Activity of Six Leukemogenic Tyrosine Kinases

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