Microphthalmia (mi) in murine mast cells: regulation of its stimuli-mediated expression on the translational level.
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.
Nechushtan
H
H
Department of Biochemistry, Hebrew University-Hadassah Medical School, Jerusalem, Israel.
Zhang
Z
Z
Razin
E
E
D000595:Amino Acid Sequence; D000818:Animals; D002460:Cell Line; D004268:DNA-Binding Proteins / Q000096:biosynthesis* / Q000235:genetics; D005786:Gene Expression Regulation; D007073:Immunoglobulin E / Q000276:immunology; D007152:Immunologic Capping; D007377:Interleukin-3 / Q000494:pharmacology; D015847:Interleukin-4 / Q000494:pharmacology; D016350:Leucine Zippers / Q000235:genetics; D008407:Mast Cells / Q000378:metabolism*; D008544:Melanocytes / Q000378:metabolism; D051379:Mice; D008822:Mice, Transgenic; D051739:Microphthalmia-Associated Transcription Factor; D008850:Microphthalmos / Q000235:genetics*; D008969:Molecular Sequence Data; D014176:Protein Biosynthesis; D011817:Rabbits; D015398:Signal Transduction; D014157:Transcription Factors / Q000378:metabolism; D014158:Transcription, Genetic; D051720:Upstream Stimulatory Factors
D004268:DNA-Binding Proteins; D007377:Interleukin-3; D051739:Microphthalmia-Associated Transcription Factor; C497235:Mitf protein, mouse; D014157:Transcription Factors; D051720:Upstream Stimulatory Factors; D015847:Interleukin-4; D007073:Immunoglobulin E