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)

Mice harboring a mutation in the microphthalmia (mi) gene display a variety of abnormalities, including microphthalmia, depletion of skin melanocytes, deafness, a defect in osteoclasts, and a major decrease in mast cell number and function. However, despite the possible critical role played by this protein in mast cell development and function, characterization of its mRNA and protein synthesis in these cells has not yet been performed. In this study, we investigated the regulation of the synthesis of mi in murine mast cells activated by various physiologic stimuli. Using a specific rabbit polyclonal anti-mi antibody, we found that interleukin-3, interleukin-4, or aggregation of the mast cell high-affinity receptor for IgE (Fc epsilonRI) induced the synthesis of mi protein in these cells. None of these stimuli significantly affected the level of mi mRNA in the mast cells at any of the time points tested. Also, using this specific anti-mi antibody, an increase in mi protein synthesis was shown during differentiation of mast cells from their bone marrow cell precursors. Moreover, a complex containing mi bound to upstream stimulating factor 2 was detected only in activated mast cells. We conclude that the regulation of mi expression is on the translational level. Thus, stimulation of mast cells by a variety of stimuli elicits a signaling pathway that regulates mi expression.
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PMID:Microphthalmia (mi) in murine mast cells: regulation of its stimuli-mediated expression on the translational level. 910 21

Mastocytosis is a disease characterized by excessive accumulation of mast cells in different tissues and symptoms caused by the release of mast cell mediators. The skin is frequently directly involved in mastocytosis. The disease is rarely seen in other members of the subjects' family; only 49 cases of familial mastocytosis have been reported. Familial mastocytosis associated with hearing loss may represent a newly described inherited entity. We describe a brother and sister exhibiting skin mastocytosis and neurosensory deafness, associated with a history of hearing loss in their father's family. The appearance of the mast cell disease in two siblings, who presented with similar clinical features represents a familial form of mastocytosis; the association with an inherited form of deafness may constitute a new syndrome. Our patients show several features similar to some previously reported cases but different insofar that additional congenital defects and mental retardation are absent.
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PMID:Familial mastocytosis associated with neurosensory deafness. 1097 97

Mutation of microphthalmia transcription factor (MITF) results in deafness, bone loss, small eyes, and poorly pigmented eyes and skin. The primary cell types affected in MITF-deficient mice are melanocytes, osteoclasts and mast cells. A search for MITF-associated proteins, using a mast cell library that was screened with a construct that encodes the basic helix-loop-helix leucine zipper (bHLH-Zip) domain of MITF, resulted in the isolation of the protein kinase C interacting (PKCI) protein 1 and protein inhibitor of activated STAT3 (PIAS3). We have accumulated clear evidence of a function for these two proteins as repressors of MITF-induced transcriptional activity. Here, we describe this evidence and ideas that give some insight into the cellular network of interactions between various transcription factors and MITF.
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PMID:The function of MITF and associated proteins in mast cells. 1221 80

Mutation of microphthalmia transcription factor (MITF) results in deafness, bone loss, small eyes, and poorly pigmented eyes and skin. A search for MITF-associated proteins, using a mast cell library that was screened with a construct that encodes the basic helix-loop-helix leucine zipper (Zip) domain of MITF, resulted in the isolation of the STAT3 inhibitor, PIAS3. PIAS3 functions in vivo as a key molecule in suppressing the transcriptional activity of MITF. Here, we report that the Zip domain is the region of MITF that is involved in the direct interaction between MITF and PIAS3. Additionally, we investigated the effect of phosphorylation of MITF on its interaction with PIAS3. We found that phosphorylation of MITF on serines in positions 73 and 409 plays an important role in its association with PIAS3. This effect was profound with phosphorylation on Ser409, which significantly reduced the inhibitory effect of PIAS3 on MITF and also modulated the transcriptional activity of MITF. Thus, phosphorylation of MITF could be considered a fine, and alternative, tuning of its transcriptional machinery.
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PMID:Role played by microphthalmia transcription factor phosphorylation and its Zip domain in its transcriptional inhibition by PIAS3. 1464 19

Manipulation of the mouse genome has emerged as an important approach for studying gene function and establishing human disease models. In this study, the mouse mutants were generated through N-ethyl-N-nitrosourea (ENU)-induced mutagenesis in C57BL/6J mice. The screening for dominant mutations yielded several mice with fur color abnormalities. One of them causes a phenotype similar to that shown by dominant-white spotting (W) allele mutants. This strain was named Wads because the homozygous mutant mice are white color, anemic, deaf, and sterile. The new mutation was mapped to 42 cM on chromosome five, where proto-oncogene c-kit resides. Sequence analysis of c-kit cDNA from Wads(m/m) revealed a unique T-to-C transition mutation that resulted in Phe-to-Ser substitution at amino acid 856 within a highly conserved tyrosine kinase domain. Compared with other c-kit mutants, Wads may present a novel loss-of-function or hypomorphic mutation. In addition to the examination of adult phenotypes in hearing loss, anemia, and mast cell deficiency, we also detected some early developmental defects during germ cell differentiation in the testis and ovary of neonatal Wads(m/m) mice. Therefore, the Wads mutant may serve as a new disease model of human piebaldism, anemia, deafness, sterility, and mast cell diseases.
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PMID:Identification of a novel point mutation of mouse proto-oncogene c-kit through N-ethyl-N-nitrosourea mutagenesis. 1573 17