{"id":{"repo_id":"uiuc","oai_identifier":"oai:www.ideals.illinois.edu:2142/72931"},"canonical_url":"https://search.dev.ndltd.org/etd/uiuc/oai:www.ideals.illinois.edu:2142/72931","repository":{"repo_id":"uiuc","name":"University of Illinois - Urbana-Champaign","base_url":"https://www.ideals.illinois.edu/oai-pmh"},"display":{"title":"SGK196 controls stem cell fates by promoting the degradation of TGFβ family receptors","abstract":"Much remains to be understood regarding the molecular mechanisms controlling stem cell fate. Through studies in human pluripotent stem cells (hPSCs), I have identified SGK196, an atypical kinase of relatively unknown function, as a novel regulator of cell fate and the TGFβ family signaling pathway. SGK196 depletion in human embryonic stem cells (hESCs) inhibits neural induction and enhances mesoderm induction, while SGK196 overexpression represses mesoderm and endoderm induction. SGK196 negatively regulates TGFβ family signaling by interacting with and promoting the degradation of TGFβ family receptors. Interactions were observed to occur within the SGK196 transmembrane (TM) domain. Mutation of specific Asn, Asp, and His residues in the SGK196 TM domain resulted in the diminished degradation of TGFβ family receptors and reduced interactions with the type I BMP receptor (BMPR1B), suggesting that these polar residues may play a key role in arbitrating SGK196 activity. The functional effects of Sgk196 in Xenopus laevis animal caps and embryos are in agreement with the results in hESCs. Defects in Sgk196 depleted Xenopus embryos include impaired development of neural tissues and increased development of mesodermal tissues. Overall, I demonstrate that SGK196 is an essential regulator of stem cell fate determination and early development. Through uncovering the regulatory mechanism of SGK196 I unveil valuable insight into receptor-level regulation of the TGFβ family pathway.","abstract_html":"Much remains to be understood regarding the molecular mechanisms controlling stem cell fate. Through studies in human pluripotent stem cells (hPSCs), I have identified SGK196, an atypical kinase of relatively unknown function, as a novel regulator of cell fate and the TGFβ family signaling pathway. SGK196 depletion in human embryonic stem cells (hESCs) inhibits neural induction and enhances mesoderm induction, while SGK196 overexpression represses mesoderm and endoderm induction. SGK196 negatively regulates TGFβ family signaling by interacting with and promoting the degradation of TGFβ family receptors. Interactions were observed to occur within the SGK196 transmembrane (TM) domain. Mutation of specific Asn, Asp, and His residues in the SGK196 TM domain resulted in the diminished degradation of TGFβ family receptors and reduced interactions with the type I BMP receptor (BMPR1B), suggesting that these polar residues may play a key role in arbitrating SGK196 activity. The functional effects of Sgk196 in Xenopus laevis animal caps and embryos are in agreement with the results in hESCs. Defects in Sgk196 depleted Xenopus embryos include impaired development of neural tissues and increased development of mesodermal tissues. Overall, I demonstrate that SGK196 is an essential regulator of stem cell fate determination and early development. Through uncovering the regulatory mechanism of SGK196 I unveil valuable insight into receptor-level regulation of the TGFβ family pathway.","abstract_has_math":false,"creators":["Tsang Mui Chung, Stephanie"],"institution":"University of Illinois at Urbana-Champaign","degree_name":"Ph.D.","degree_level":"Dissertation","degree_discipline":"Cell and Developmental Biology","degree_department":null,"school":null,"contributors":["Chen, Jie","Belmont, Andrew S.","Bolton, Eric","Henry, Jonathan"],"advisors":[],"committee_chairs":[],"committee_members":[],"year":2015,"date_issued":"2015-01-21T19:49:35Z","date_published":"2015-01-21T19:49:35Z","updated_at":"2026-07-22T22:26:07Z","subjects":["SGK196","cell signaling","TGFβ family signaling pathway","transmembrane domain","human embryonic stem cells","cell fate"],"languages":["en"],"rights":["Copyright 2014 Stephanie Tsang Mui Chung"],"rights_urls":[],"identifier_entries":[]},"links":{"outbound_url":"http://hdl.handle.net/2142/72931","outbound_label":"Handle","outbound_source":"dc:identifier"},"metadata_groups":[{"id":"people","label":"People","entries":[{"key":"dc:contributor","label":"Contributor","values":["Chen, Jie","Belmont, Andrew S.","Bolton, Eric","Henry, Jonathan"]},{"key":"dc:creator","label":"Author","values":["Tsang Mui Chung, Stephanie"]}]},{"id":"academic_context","label":"Academic Context","entries":[{"key":"dc:date","label":"Dc Date","values":["2015-01-21T19:49:35Z","2014-12","2015-01-21"]},{"key":"dc:type","label":"Dc Type","values":["text"]},{"key":"thesis:degree_discipline","label":"Discipline","values":["Cell and Developmental Biology"]},{"key":"thesis:degree_level","label":"Degree Level","values":["Dissertation"]},{"key":"thesis:degree_name","label":"Degree Name","values":["Ph.D."]},{"key":"thesis:institution_name","label":"Thesis Institution Name","values":["University of Illinois at Urbana-Champaign"]}]},{"id":"subjects_keywords","label":"Subjects and Keywords","entries":[{"key":"dc:subject","label":"Dc Subject","values":["SGK196","cell signaling","TGFβ family signaling pathway","transmembrane domain","human embryonic stem cells","cell fate"]}]},{"id":"language_rights","label":"Language and Rights","entries":[{"key":"dc:language","label":"Dc Language","values":["en"]},{"key":"dc:rights","label":"Dc Rights","values":["Copyright 2014 Stephanie Tsang Mui Chung"]}]},{"id":"identifiers","label":"Identifiers","entries":[{"key":"dc:identifier","label":"Identifier","values":["http://hdl.handle.net/2142/72931"]}]},{"id":"additional","label":"Additional Metadata","entries":[{"key":"dc:description","label":"Description","values":["Much remains to be understood regarding the molecular mechanisms controlling stem cell fate. Through studies in human pluripotent stem cells (hPSCs), I have identified SGK196, an atypical kinase of relatively unknown function, as a novel regulator of cell fate and the TGFβ family signaling pathway. SGK196 depletion in human embryonic stem cells (hESCs) inhibits neural induction and enhances mesoderm induction, while SGK196 overexpression represses mesoderm and endoderm induction. SGK196 negatively regulates TGFβ family signaling by interacting with and promoting the degradation of TGFβ family receptors. Interactions were observed to occur within the SGK196 transmembrane (TM) domain. Mutation of specific Asn, Asp, and His residues in the SGK196 TM domain resulted in the diminished degradation of TGFβ family receptors and reduced interactions with the type I BMP receptor (BMPR1B), suggesting that these polar residues may play a key role in arbitrating SGK196 activity. The functional effects of Sgk196 in Xenopus laevis animal caps and embryos are in agreement with the results in hESCs. Defects in Sgk196 depleted Xenopus embryos include impaired development of neural tissues and increased development of mesodermal tissues. Overall, I demonstrate that SGK196 is an essential regulator of stem cell fate determination and early development. Through uncovering the regulatory mechanism of SGK196 I unveil valuable insight into receptor-level regulation of the TGFβ family pathway.","Item withdrawn by Mark Zulauf (zulauf@illinois.edu) on 2014-11-20T17:22:46Z Item was in collections: University of Illinois Theses & Dissertations (ID: 1) No. of bitstreams: 2 Tsang Mui Chung_Stephanie.docx: 14569941 bytes, checksum: d01dea1d43f6301e87cf26db50858d46 (MD5) Tsang Mui Chung_Stephanie.pdf: 11776668 bytes, checksum: d878f7435095e814f4ae8e50c1a2f628 (MD5)","Made available in DSpace on 2015-01-21T19:49:35Z (GMT). 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SGK196 depletion in human embryonic stem cells (hESCs) inhibits neural induction and enhances mesoderm induction, while SGK196 overexpression represses mesoderm and endoderm induction. SGK196 negatively regulates TGFβ family signaling by interacting with and promoting the degradation of TGFβ family receptors. Interactions were observed to occur within the SGK196 transmembrane (TM) domain. Mutation of specific Asn, Asp, and His residues in the SGK196 TM domain resulted in the diminished degradation of TGFβ family receptors and reduced interactions with the type I BMP receptor (BMPR1B), suggesting that these polar residues may play a key role in arbitrating SGK196 activity. The functional effects of Sgk196 in Xenopus laevis animal caps and embryos are in agreement with the results in hESCs. Defects in Sgk196 depleted Xenopus embryos include impaired development of neural tissues and increased development of mesodermal tissues. Overall, I demonstrate that SGK196 is an essential regulator of stem cell fate determination and early development. Through uncovering the regulatory mechanism of SGK196 I unveil valuable insight into receptor-level regulation of the TGFβ family pathway.","Item withdrawn by Mark Zulauf (zulauf@illinois.edu) on 2014-11-20T17:22:46Z Item was in collections: University of Illinois Theses & Dissertations (ID: 1) No. of bitstreams: 2 Tsang Mui Chung_Stephanie.docx: 14569941 bytes, checksum: d01dea1d43f6301e87cf26db50858d46 (MD5) Tsang Mui Chung_Stephanie.pdf: 11776668 bytes, checksum: d878f7435095e814f4ae8e50c1a2f628 (MD5)","Made available in DSpace on 2015-01-21T19:49:35Z (GMT). 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