Selective regulation of BMP4 signaling by the receptor tyrosine kinase MuSK

Yilmaz, Atilgan

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Year:: 2013
Contributor:: Yilmaz, Atilgan (creator); Fallon, Justin (Director); Wharton, Kristi (Reader); Barnea, Gilad (Reader); Zervas, Mark (Reader); Burden, Steven (Reader); Brown University. BIOMED: Molecular Biology, Cell Biology, and Biochemistry (sponsor)
Genre:: theses
Subject:: MuSK; BMP4; BMP pathway; biglycan; DMD
Extent:: xxiii, 292 p.
DOI: https://doi.org/10.7301/Z037772V

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Abstract:: Communication between the extracellular matrix and the intracellular environments of the cells is crucial for multiple processes such as survival, proliferation or maintenance of cellular states. Failure or mistakes in this communication leads to inability to form subcellular organizations or to give appropriate responses to the changes in the cellular environment or several disease states such as cancer. Therefore it is important to understand how cells employ different mechanisms to relay information from the extracellular matrix to their cytoplasm. One common way of such communication is established by the use of signaling molecules that are recognized by their receptors at the cell surface and the signaling cascades initiated by this receptor-ligand interaction. This mechanism is key to both the intercellular communication and the autocrine regulatory events. In this thesis I discuss two examples of interactions between signaling pathways, as well as mechanisms in which extracellular molecules regulate cytosolic proteins. The first project details the studies based on an incidental observation showing that the receptor tyrosine kinase MuSK and the signaling molecule BMP4 bind to each other. I also demonstrate how the muscle-specific receptor tyrosine kinase MuSK regulates BMP4 signaling in muscle cells (Chapter 2). The results of these studies show that MuSK binds to BMP4 and is required for the transcription of a subset of genes in response to BMP4. In Chapter 3, I demonstrate a role for BMP4 in the induction of AChR clusters in cultured muscle cells. My results suggest that this BMP4 effect requires MuSK and Wnt11 activities. In the last data chapter, I present the work detailing biglycan's regulation of sarcolemmal utrophin expression, the therapeutic effect of this regulation for Duchenne Muscular Dystrophy (DMD) and the mechanisms thereof (Chapter 4). Finally, I discuss the importance of these findings and the future directions (Chapter 5).
Notes:: Thesis (Ph.D. -- Brown University (2013)

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Yilmaz, Atilgan, "Selective regulation of BMP4 signaling by the receptor tyrosine kinase MuSK" (2013). Molecular Biology, Cell Biology, and Biochemistry Theses and Dissertations. Brown Digital Repository. Brown University Library. https://doi.org/10.7301/Z037772V

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Molecular Biology, Cell Biology, and Biochemistry Theses and Dissertations

Theses and Dissertations for the Molecular Biology, Cell Biology, and Biochemistry department.
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