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A lentiviral screen for novel regulators of IL-7R[alpha] in a pre-B cell line

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dc.contributor.advisor Jianzhu Chen. en_US Trajman, Lily Christine en_US
dc.contributor.other Massachusetts Institute of Technology. Dept. of Biology. en_US 2009-10-01T15:58:33Z 2009-10-01T15:58:33Z 2009 en_US 2009 en_US
dc.description Thesis (Ph. D.)--Massachusetts Institute of Technology, Dept. of Biology, 2009. en_US
dc.description In title on title page, [alpha] appears as lower case Greek letter. en_US
dc.description Includes bibliographical references. en_US
dc.description.abstract IL-7R[alpha] is one component of the heterodimeric IL-7R[alpha] receptor, and signaling through this receptor is essential for murine T and B cell development as well as human T cell development. IL-7R[alpha] signaling is also responsible for homeostatic proliferation of T cells in lymphopenic hosts, as well as maintenance of naïve and memory CD8+ T cells in the periphery. A number of regulators of IL-7R[alpha][alpha] have been identified, but the complex processes underlying fine control of IL-7R[alpha][alpha] expression are poorly understood. The RNAi Consortium's lentivirus-based shRNA library targeting murine kinases and phosphatases has allowed large scale screening for modulators of IL-7R[alpha][alpha] surface expression. This library provides shRNAs in the pLKO. 1 lentiviral vector targeting 1278 known kinases and phosphatases. Analysis of the FACS-based assay identified 38 potential regulators of IL-7R[alpha][alpha] in a pre-B cell line. Subsequent validation of five of the hits confirmed known pathways of IL-7R regulation and also pointed to new potential points of regulatory control. Phosphoinositide 3-kinase (PI3K) regulates a number of cell signaling pathways that promote survival, proliferation and increased metabolism. In mammals the Class I family of PI3Ks consists of four different catalytic subunits, which can pair with any of six different regulatory subunits. PI3K was recently shown to regulate the expression of the interleukin-7 receptor alpha chain (IL-7R[alpha][alpha]) via the Foxol transcription factor. en_US
dc.description.abstract (cont.) Because IL-7R signaling is vital for murine B and T cell development, cells use a variety of mechanisms to maintain tight control of the expression of IL-7R[alpha][alpha]. Here we utilize sequential knockdown of the four Class I PI3K catalytic subunits to demonstrate that each plays a distinct role in separate pathways leading to the activation of Akt and the expression of total Foxol protein. en_US
dc.description.statementofresponsibility by Lily Christine Trajman. en_US
dc.format.extent 189 leaves en_US
dc.language.iso eng en_US
dc.publisher Massachusetts Institute of Technology en_US
dc.rights M.I.T. theses are protected by copyright. They may be viewed from this source for any purpose, but reproduction or distribution in any format is prohibited without written permission. See provided URL for inquiries about permission. en_US
dc.rights.uri en_US
dc.subject Biology. en_US
dc.title A lentiviral screen for novel regulators of IL-7R[alpha] in a pre-B cell line en_US
dc.type Thesis en_US Ph.D. en_US
dc.contributor.department Massachusetts Institute of Technology. Dept. of Biology. en_US
dc.identifier.oclc 433146521 en_US

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