Disease relevance of Csf2ra

• Our findings provide evidence that a defect in the expression of betac or betac plus GM-CSFR alpha on AML blasts can be associated with respiratory failure in patients with AML [1].
• In addition, although some murine T lymphomas can express the GM-CSF receptor, none of the human cell lines of T cell lineage that we examined bound iodinated human GM-CSF [2].
• Human GM-CSF also bound to primary human monocytes and to the myelogenous leukemia cell line, KG-1, but not to any of the murine cells known to express the murine GM-CSF receptor [2].
• However, because huGM-CSF does not react with the murine GM-CSF receptor possible side-effects to nonleukemic tissues could not be analyzed in the AML/SCID model [3].
• GM-CSF expression was detected in 13 of 30 squamous cell carcinoma specimens (43%) and GM-CSFR expression was detected in 10 specimens (33%) [4].

High impact information on Csf2ra

• Our data indicate that activation of the GM-CSF receptor induces differentiation of stem cells by an instructive mechanism that can be blocked by the activated IL-3 receptor [5].
• Chimaeric IL-2 receptor beta and gamma chains constructed with the heterodimeric extracellular regions of the granulocyte-macrophage colony stimulating factor receptor (GM-CSFR) also provided the IL-2R signal [6].
• Engagement of IL3-R and GM-CSF-R in these cells leads to increased and prolonged PI3'K-dependent PI(3,4,5)P3 accumulation and PKB activation [7].
• However, mice in which the genes encoding GM-CSF (Gmcsf) or the beta common subunit of the GM-CSF receptor (betac) are inactivated display normal steady-state hematopoiesis [8].
• GM-CSF receptor immunoreactivity was found on neurons within the paraventricular and arcuate nuclei of the hypothalamus [9].

Chemical compound and disease context of Csf2ra

• Analysis of various mutants of the cytoplasmic region of GM-CSFR indicated that both the conserved membrane proximal region and tyrosine residues located in the distal part of the beta subunit were required for HIV-1 LTR activation [10].

Biological context of Csf2ra

• Although the signal transduction pathways triggered by GM-CSF receptor (GMR) have been extensively characterized, the roles of GMR signals in differentiation have remained to be elucidated [11].
• Granulocyte macrophage colony-stimulating factor (GM-CSF) binds to the high-affinity GM-CSF receptor (GMR) consisting of alpha and beta subunits and induces rapid tyrosine phosphorylation, activation of early response genes, and proliferation of hematopoietic cells [12].
• Cumulus-oocyte complexes from both genotypes were found to express mRNA for the GM-CSFRalpha-subunit only, while the mural granulosa cells expressed both the alpha and beta receptor subunits [13].
• Zidovudine (AZT) treatment suppresses granulocyte-monocyte colony stimulating factor receptor type alpha (GM-CSFR alpha) gene expression in murine bone marrow cells [14].
• Common laboratory strains such as C57BL/6J carry a single Csf2ra gene that maps to the distal end of Chromosome (Chr) 19 [15].

Anatomical context of Csf2ra

• A truncated STAT3, which acts in a dominant negative manner was introduced into WEHI-3B D+ cells expressing GM-CSFRalpha-LIFR and GM-CSFRbetac-LIFR [16].
• This occurs despite an apparent requirement of these mutants for the GM-CSF receptor alpha-subunit (GMRalpha), which is not expressed in CFU-E [17].
• Cells expressing GM-CSF receptor were identified as macrophages, granulocytes and putative dendritic cells by flow cytometric analysis using lineage and receptor subunit specific antibodies [18].
• GM-CSF receptor mRNA was present in the fertilized oocyte and all subsequent stages of development, and in blastocysts it was expressed in both inner cell mass and trophectoderm cells [19].
• The present studies indicate that the GM-CSF receptor expressed on CFU-GM and mature myeloid cells are structurally similar [20].

Associations of Csf2ra with chemical compounds

• In conclusion, these data indicate that GM-CSF signaling through the low-affinity GM-CSF receptor in blastocysts is associated with increased glucose uptake and enhanced proliferation and/or viability of blastomeres [19].

Physical interactions of Csf2ra

• The biologic actions of GM-CSF are mediated by its binding to the alpha and beta subunits of the GM-CSF receptor (GM-CSFRalpha and betac, respectively) [21].

Regulatory relationships of Csf2ra

• Granulocyte-macrophage colony-stimulating factor (GM-CSF) and inflammatory stimuli up-regulate secretion of the soluble GM-CSF receptor in human monocytes: evidence for ectodomain shedding of the cell surface GM-CSF receptor alpha subunit [22].

Other interactions of Csf2ra

• These results indicate that the beta subunit of the GM-CSF receptor is required for generation of growth signals and that AIC2B is likely the beta subunit of the mouse GM-CSF receptor [23].
• This technology has been applied to the study of interactions between human granulocyte-macrophage colony-stimulating factor (GM-CSF) and its receptor (GM-CSFR) [24].
• Regulation of IL-5R alpha, IL-3R alpha and GM-CSFR alpha expression in the developmental stage appears to be important for understanding the unique function of these cytokines on a particular cell type [25].
• Developmental expression of Magmas in murine tissues and its co-expression with the GM-CSF receptor [26].
• A maximum reduction in GM-CSF receptor numbers of 65% to 77% was observed by 96-hour incubation with TGF-beta [27].

Analytical, diagnostic and therapeutic context of Csf2ra

• 2 and 3 additionally lacked the expression of GM-CSFR alpha, as shown by flow cytometry [1].
• Expression of GM-CSF receptor (GM-CSFR) alpha and beta mRNA subunits by cumulus-oocyte complexes and mural granulosa cells was examined using RT-PCR [13].
• Using interspecific backcross mapping and in situ hybridization, we demonstrate that one of these species, Mus spretus, carries four Csf2ra genes dispersed among the distal tips of Chrs 4, 10, 13, and 19 [15].
• Site-directed mutagenesis of tyrosine-750 (Y750), which is contained within the distal viability domain, to phenylalanine eliminates all demonstrable tyrosine phosphorylation of GMR beta [28].
• Molecular cloning of a second subunit of the receptor for human granulocyte-macrophage colony-stimulating factor (GM-CSF): reconstitution of a high-affinity GM-CSF receptor [29].

References