Gene/Protein Disease Symptom Drug Enzyme Compound
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Query: UNIPROT:P15088 (mast cell)
 14,925 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

Stem cell factor (SCF) is encoded at the Sl locus of the mouse and is the ligand for the c-kit receptor. Recombinant rat SCF164 (rrSCF164) induces proliferation and promotes maturation of mouse mast cells in vitro and in vivo and can also induce c-kit receptor-dependent mouse mast cell degranulation. We now report that in both quiescent and non-quiescent mouse bone marrow-derived cultured mast cells (BMCMC) rrSCF164 induces increased mRNA levels for the "early response genes" c-fos, c-jun and junB but has only slight effects on the expression of junD. Recombinant mouse interleukin-3 (IL-3) also promotes proliferation of both quiescent and non-quiescent BMCMC. However, IL-3 induces increased expression of c-fos and junB only in quiescent BMCMC. Cross-linking of Fc epsilon receptor type I (Fc epsilon RI) on BMCMC by IgE and specific antigen induces a pattern of early gene expression very similar to that induced by rrSCF164. However, BMCMC stimulated through the Fc epsilon RI did not proliferate and, in comparison to control BMCMC, exhibited significantly decreased proliferation in response to rrSCF164 or IL-3. These results indicate that stimulation of BMCMC proliferation by IL-3 or rrSCF164 induces distinct patterns of early response gene expression and suggest that the proliferative effects of these growth factors may be mediated through distinct signal transduction pathways. Our data also point to previously unappreciated similarities between the effects of signaling through the c-kit receptor or the Fc epsilon RI on mast cell expression of fos and jun genes.
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PMID:Distinct patterns of early response gene expression and proliferation in mouse mast cells stimulated by stem cell factor, interleukin-3, or IgE and antigen. 768

Serum induces the expression of the fos and jun gene families, which encode the transcription factor AP-1. Since we previously found that activation of mast cells by IgE-antigen (Ag) induces the mRNA accumulation of c-fos, c-jun, junB and junD proto-oncogenes, we were prompted to investigate whether serum could affect such accumulation in these cells. In addition, we investigated whether serum could modulate inhibition of DNA synthesis in immunologically stimulated mast cells. Mast cells, which were cultured in the presence of fetal calf serum (FCS), were characterized by a high proliferation rate and high accumulation of the mRNA of c-fos, junB and junD proto-oncogenes. After sustained FCS deprivation both DNA synthesis and the level of c-fos mRNA were significantly decreased, as expected, whereas the level of c-jun, junB and junD mRNA were not affected. As opposed to mast cells which were cultured in the presence of FCS, immunological stimulation of FCS-deprived cells resulted in DNA synthesis inhibition and an increase in c-fos expression. The results also show that the level of c-fos mRNA was increased by either IgE-Ag or FCS up to a similar level, while these two triggers could not act synergistically to enhance this expression further. Thus, changes in DNA synthesis, induced by FCS, block the ability of the immunological challenge to inhibit mast cell growth and to enhance c-fos mRNA accumulation.
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PMID:Serum modulates mast cell responses to IgE antigen stimulation. 841 82

Murine bone marrow-derived cultured mast cells (BMMCs) are most widely used in in vitro experiments for evaluation of mast cell functions. The present study has shown that cell preparation procedure, i.e., cell collection by centrifugation and the subsequent adjustment and culture of cell density at the desired concentrations, transiently induced gene expression of plasminogen activator inhibitor-1 (PAI-1) and the AP-1 components (c-fos, c-jun, and junB). The level of PAI-1 gene transcript was closely related to the cell density and the gene expression was enhanced by pretreatment with okadaic acid, an inhibitor of protein phosphatases 1 (PP1) and 2A (PP2A). The cell preparation procedure also caused dephosphorylation of MAP kinases, i.e., ERK, p38, and JNK, resulting from PP1/PP2A activation. In view of the cell responses to the cell preparation procedure itself, care is needed in the interpretation of in vitro data using BMMCs.
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PMID:Responses during cell preparation for functional analyses in mouse bone marrow-derived cultured mast cells. 1647 20

Bcl2 family proteins control mitochondrial apoptosis and its members exert critical cell type and differentiation stage-specific functions, acting as barriers against autoimmunity or transformation. Anti-apoptotic Bcl2a1/Bfl1/A1 is frequently deregulated in different types of blood cancers in humans but its physiological role is poorly understood as quadruplication of the Bcl2a1 gene locus in mice hampers conventional gene targeting strategies. Transgenic overexpression of A1, deletion of the A1-a paralogue or constitutive knockdown in the hematopoietic compartment of mice by RNAi suggested rate-limiting roles in lymphocyte development, granulopoiesis and mast cell activation. Here we report on the consequences of conditional knockdown of A1 protein expression using a reverse transactivator (rtTA)-driven approach that highlights a critical role for this Bcl2 family member in the maintenance of mature B-cell homeostasis. Furthermore, we define the A1/Bim (Bcl-2 interacting mediator of cell death) axis as a target of key kinases mediating B-cell receptor (BCR)-dependent survival signals, such as, spleen tyrosine kinase (Syk) and Brutons tyrosine kinase (Btk). As such, A1 represents a putative target for the treatment of B-cell-related pathologies depending on hyperactivation of BCR-emanating survival signals and loss of A1 expression accounts, in part, for the pro-apoptotic effects of Syk- or Btk inhibitors that rely on the 'BH3-only' protein Bim for cell killing.
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PMID:Conditional knockdown of BCL2A1 reveals rate-limiting roles in BCR-dependent B-cell survival. 2645 Apr 54