2026-09-20T19:17:07Zhttps://dspace.mit.edu/server/oai/requestoai:dspace.mit.edu:1721.1/478852022-01-13T07:54:15Zcom_1721.1_7582com_1721.1_7581col_1721.1_131022
Jianzhu Chen.
Trajman, Lily Christine
Massachusetts Institute of Technology. Dept. of Biology.
Massachusetts Institute of Technology. Department of Biology
2009-10-01T15:58:33Z
2009-10-01T15:58:33Z
2009
2009
http://hdl.handle.net/1721.1/47885
433146521
Thesis (Ph. D.)--Massachusetts Institute of Technology, Dept. of Biology, 2009.
In title on title page, [alpha] appears as lower case Greek letter.
Includes bibliographical references.
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.
(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.
by Lily Christine Trajman.
Ph.D.
189 leaves
eng
Massachusetts Institute of Technology
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.
http://dspace.mit.edu/handle/1721.1/7582
Biology.
A lentiviral screen for novel regulators of IL-7R[alpha] in a pre-B cell line
Thesis
application/pdf
false
Publication
unknown
unknown
<Publication xmlns="https://www.openaire.eu/cerif-profile/1.1/" id="31caaea4-afcb-46c5-898b-aa8d6b5bd2be">
<Type xmlns="https://www.openaire.eu/cerif-profile/vocab/COAR_Publication_Types">http://purl.org/coar/resource_type/c_1843</Type>
<Language>eng</Language>
<Title>A lentiviral screen for novel regulators of IL-7R[alpha] in a pre-B cell line</Title>
<PublishedIn>
<Publication>
</Publication>
</PublishedIn>
<PublicationDate>2009</PublicationDate>
<Authors>
<Author>
<DisplayName>Trajman, Lily Christine</DisplayName>
<Affiliation>
<OrgUnit>
</OrgUnit>
</Affiliation>
</Author>
</Authors>
<Editors>
</Editors>
<Publishers>
<Publisher>
<DisplayName>Massachusetts Institute of Technology</DisplayName>
<OrgUnit />
</Publisher>
</Publishers>
<License>http://dspace.mit.edu/handle/1721.1/7582</License>
<Keyword>Biology.</Keyword>
<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.</Abstract>
<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.</Abstract>
<Access xmlns="http://purl.org/coar/access_right"
>
</Access>
</Publication>