Lasting B-cell persistence depends on survival signals that are transduced by cell surface receptors. Here, we describe a novel biological mechanism essential for survival and homeostasis of normal peripheral mature B cells and chronic lymphocytic leukemia (CLL) cells, regulated by the heparin-binding cytokine, midkine (MK), and its proteoglycan receptor, the receptor-type tyrosine phosphatase zeta (RPTP). We demonstrate that MK initiates a signaling cascade leading to B cell survival, by binding to RPTP. In mice lacking PTPRZ, the proportion and number of the mature B cell population is reduced. Our results emphasize a unique and critical function for MK signaling in the previously described MIF/CD74 induced survival pathway. Stimulation of CD74 with MIF leads to c-Met activation, resulting in elevation of MK expression in both normal mouse splenic B and CLL cells. Our results indicate that MK and RPTP are important regulators of the B cell repertoire. These findings could pave the way towards understanding the mechanisms shaping B cell survival, and suggest novel therapeutic strategies based on the blockade of the midkine/RPTP-dependent survival pathway.
The cytokine midkine and its receptor RPTPζ regulate B cell survival in a pathway induced by CD74.
Age
View SamplesWe measured gene expression in the adrenal glands of the Spontaneously Hypertensive Rat (SHR) and Wistar-Kyoto rat (WKY) using Affymetrix RG-U34A GeneChips. All rats were aged-matched at 4-weeks. The rats were obtained from the colonies at the Univeristy of California San Diego, La Jolla, CA.
Common genetic mechanisms of blood pressure elevation in two independent rodent models of human essential hypertension.
No sample metadata fields
View SamplesWe performed Affymetrix MG-U74Av2 GeneChip experiements on mRNA from the adrenal glands of the BPH hypertensive and BPL hypotensive mouse strains. All mice were aged-matched at 5 weeks. We obtained the mice from Jackson Laboratories, Bar Harbor, ME.
Neuroendocrine transcriptome in genetic hypertension: multiple changes in diverse adrenal physiological systems.
No sample metadata fields
View SamplesThis SuperSeries is composed of the SubSeries listed below.
Global metabolic consequences of the chromogranin A-null model of hypertension: transcriptomic detection, pathway identification, and experimental verification.
Sex, Specimen part
View SamplesThe objective of the experiment is to determine the genes differentially expressed in the liver of the chromogranin A knockout mouse (Mahapatra et al., 2005).
Global metabolic consequences of the chromogranin A-null model of hypertension: transcriptomic detection, pathway identification, and experimental verification.
Sex, Specimen part
View SamplesThe objective of the experiment is to determine the genes differentially expressed in the adrenal gland of the chromogranin A knockout mouse (Mahapatra et al., 2005).
Global metabolic consequences of the chromogranin A-null model of hypertension: transcriptomic detection, pathway identification, and experimental verification.
Sex, Specimen part
View SamplesWe demonstrated that 3-Deazaneplanocin A (DZNep), a histone methyltransferase inhibitor, induce robust apoptosis in AML cells through increased ROS production and ER stress.
The histone methyltransferase inhibitor, DZNep, up-regulates TXNIP, increases ROS production, and targets leukemia cells in AML.
Cell line
View SamplesFor the microarray experiments, MV4-11 and MOLM-14 cells were treated with DMSO control, ABT-869 3 nM, SAHA 6 uM and combination therapy for 24 hours. Cells were then washed in PBS and high-quality total RNA was extracted RNeasy Midi Kit, according to the manufacturers instruction (Qiagen, Valencia, USA). RNA quantity, quality, and purity were assessed with the use of the RNA 6000 Nano assay on the Agilent 2100 Bioanalyzer (Agilent Technologies, Santa Clara CA, USA). Gene expression profiling was performed using Affymetric U133plus2.0 gene chip (Affymetrix, Santa Clara, CA, USA) according to the manufacturers protocol.
PRL-3, a metastasis associated tyrosine phosphatase, is involved in FLT3-ITD signaling and implicated in anti-AML therapy.
Specimen part, Cell line
View SamplesWe found that auxin stimulates gene expression of DWF4, which encodes a rate-dertermining step in brassinosteroid biosynthesis pathways. This increased gene expressioin subsequently led to elevation of the biosynthetic flux in Arabidopsis roots.
Auxin stimulates DWARF4 expression and brassinosteroid biosynthesis in Arabidopsis.
No sample metadata fields
View SamplesWe used microarrays to examine the impact of AF1q/MLLT11 on the gene expression profile of CD34+CD45RA-Lin- and CD34+CD45RA+Lin- HPCs isolated from umbilical cord blood
AF1q/MLLT11 regulates the emergence of human prothymocytes through cooperative interaction with the Notch signaling pathway.
Specimen part
View Samples