Deletion of PDK1 Caused Cardiac Malmorphogenesis and Heart Defects Due to Profound Protein Phosphorylation Changes Mediated by SHP2
Phosphoinositide-dependent protein kinase-1 (PDK 1 ), a master kinase and involved in multiple signaling transduction, participates in regulating embryonic cardiac development and postnatal cardiac remodeling. Germline PDK 1 knockout mice displayed no heart development; in this article, we deleted P...
Gespeichert in:
| Veröffentlicht in: | Journal of cardiovascular translational research 2023-10, Vol.16 (5), p.1220-1231 |
|---|---|
| Hauptverfasser: | , , , , , |
| Format: | Artikel |
| Sprache: | eng |
| Schlagworte: | |
| Online-Zugang: | Volltext |
| Tags: |
Tag hinzufügen
Keine Tags, Fügen Sie den ersten Tag hinzu!
|
| container_end_page | 1231 |
|---|---|
| container_issue | 5 |
| container_start_page | 1220 |
| container_title | Journal of cardiovascular translational research |
| container_volume | 16 |
| creator | Luo, Hongmei Yang, Zhongzhou Li, Jie Jin, Hengwei Jiang, Mingyang Shan, Congjia |
| description | Phosphoinositide-dependent protein kinase-1 (PDK
1
), a master kinase and involved in multiple signaling transduction, participates in regulating embryonic cardiac development and postnatal cardiac remodeling. Germline PDK
1
knockout mice displayed no heart development; in this article, we deleted PDK
1
in heart tissue with different cre to characterize the temporospatial features and find the relevance with congenital heart disease(CHD), furthermore to investigate the underlying mechanism. Knocking out PDK
1
with Nkx2.5-cre, the heart showed prominent pulmonic stenosis. Ablated PDK
1
with Mef2c
SHF
-cre, the second heart field (SHF) exhibited severe hypoplasia. And deleted PDK
1
with αMHC-cre, the mice displayed dilated heart disease, protein analysis indicated PI3K and ERK were activated; meanwhile, PDK
1
-AKT-GSK3, and S6K-S6 were disrupted; phosphorylation level of Akt
473
, S6k
421/424
, and Gsk3
α21
enhanced; however, Akt
308
, S6k
389
, and Gsk3
β9
decreased. In mechanism investigation, we found SHP
2
membrane localization and phosphorylation level of SHP2
542
elevated, which suggested SHP
2
likely mediated the disruption.
Graphical abstract |
| doi_str_mv | 10.1007/s12265-023-10380-y |
| format | Article |
| fullrecord | <record><control><sourceid>proquest_cross</sourceid><recordid>TN_cdi_proquest_miscellaneous_2792501240</recordid><sourceformat>XML</sourceformat><sourcesystem>PC</sourcesystem><sourcerecordid>2792501240</sourcerecordid><originalsourceid>FETCH-LOGICAL-c324t-8e5cc12c8cb5d9712c4e1a3dc2f7cb406257ea5d8aba112857fb7b3fd015f02f3</originalsourceid><addsrcrecordid>eNp9ULtOwzAUjRBIlMIPMHlkCfgR18mIEqCIVkQCZstxrttUaVzsZMjMj2MaxMh0j3TPQ-dE0TXBtwRjcecJpQseY8piglmK4_EkmpGMiZizjJ_-4VScRxfe7zBeUCzELPoqoIW-sR2yBpXFC0G5GjzU4bi6URqtVbu37rC1G-jANx6prkZLUK5HBRjQvUfFAKi3qHTW2CF8A-ih6VC5tT4I3diqY0K-Vd0GPFpDcO5DRjWit2VJL6Mzo1oPV793Hn08Przny3j1-vSc369izWjSxylwrQnVqa54nYmAEiCK1ZoaoaskNOICFK9TVSlCaMqFqUTFTI0JN5gaNo9uJt-Ds58D-F7uG6-hbVUHdvCSioxyTGiCA5VOVO2s9w6MPLhmr9woCZY_i8tpcRkWl8fF5RhEbBL5QA5NndzZwXWh0n-qb5-UhaE</addsrcrecordid><sourcetype>Aggregation Database</sourcetype><iscdi>true</iscdi><recordtype>article</recordtype><pqid>2792501240</pqid></control><display><type>article</type><title>Deletion of PDK1 Caused Cardiac Malmorphogenesis and Heart Defects Due to Profound Protein Phosphorylation Changes Mediated by SHP2</title><source>Springer Online Journals Complete</source><creator>Luo, Hongmei ; Yang, Zhongzhou ; Li, Jie ; Jin, Hengwei ; Jiang, Mingyang ; Shan, Congjia</creator><creatorcontrib>Luo, Hongmei ; Yang, Zhongzhou ; Li, Jie ; Jin, Hengwei ; Jiang, Mingyang ; Shan, Congjia</creatorcontrib><description>Phosphoinositide-dependent protein kinase-1 (PDK
1
), a master kinase and involved in multiple signaling transduction, participates in regulating embryonic cardiac development and postnatal cardiac remodeling. Germline PDK
1
knockout mice displayed no heart development; in this article, we deleted PDK
1
in heart tissue with different cre to characterize the temporospatial features and find the relevance with congenital heart disease(CHD), furthermore to investigate the underlying mechanism. Knocking out PDK
1
with Nkx2.5-cre, the heart showed prominent pulmonic stenosis. Ablated PDK
1
with Mef2c
SHF
-cre, the second heart field (SHF) exhibited severe hypoplasia. And deleted PDK
1
with αMHC-cre, the mice displayed dilated heart disease, protein analysis indicated PI3K and ERK were activated; meanwhile, PDK
1
-AKT-GSK3, and S6K-S6 were disrupted; phosphorylation level of Akt
473
, S6k
421/424
, and Gsk3
α21
enhanced; however, Akt
308
, S6k
389
, and Gsk3
β9
decreased. In mechanism investigation, we found SHP
2
membrane localization and phosphorylation level of SHP2
542
elevated, which suggested SHP
2
likely mediated the disruption.
Graphical abstract</description><identifier>ISSN: 1937-5387</identifier><identifier>EISSN: 1937-5395</identifier><identifier>DOI: 10.1007/s12265-023-10380-y</identifier><language>eng</language><publisher>New York: Springer US</publisher><subject>Biomedical Engineering and Bioengineering ; Biomedicine ; Cardiology ; Human Genetics ; Medicine ; Medicine & Public Health ; Original Article</subject><ispartof>Journal of cardiovascular translational research, 2023-10, Vol.16 (5), p.1220-1231</ispartof><rights>The Author(s), under exclusive licence to Springer Science+Business Media, LLC, part of Springer Nature 2023. Springer Nature or its licensor (e.g. a society or other partner) holds exclusive rights to this article under a publishing agreement with the author(s) or other rightsholder(s); author self-archiving of the accepted manuscript version of this article is solely governed by the terms of such publishing agreement and applicable law.</rights><lds50>peer_reviewed</lds50><woscitedreferencessubscribed>false</woscitedreferencessubscribed><citedby>FETCH-LOGICAL-c324t-8e5cc12c8cb5d9712c4e1a3dc2f7cb406257ea5d8aba112857fb7b3fd015f02f3</citedby><cites>FETCH-LOGICAL-c324t-8e5cc12c8cb5d9712c4e1a3dc2f7cb406257ea5d8aba112857fb7b3fd015f02f3</cites><orcidid>0000-0002-6326-2118</orcidid></display><links><openurl>$$Topenurl_article</openurl><openurlfulltext>$$Topenurlfull_article</openurlfulltext><thumbnail>$$Tsyndetics_thumb_exl</thumbnail><linktopdf>$$Uhttps://link.springer.com/content/pdf/10.1007/s12265-023-10380-y$$EPDF$$P50$$Gspringer$$H</linktopdf><linktohtml>$$Uhttps://link.springer.com/10.1007/s12265-023-10380-y$$EHTML$$P50$$Gspringer$$H</linktohtml><link.rule.ids>315,781,785,27929,27930,41493,42562,51324</link.rule.ids></links><search><creatorcontrib>Luo, Hongmei</creatorcontrib><creatorcontrib>Yang, Zhongzhou</creatorcontrib><creatorcontrib>Li, Jie</creatorcontrib><creatorcontrib>Jin, Hengwei</creatorcontrib><creatorcontrib>Jiang, Mingyang</creatorcontrib><creatorcontrib>Shan, Congjia</creatorcontrib><title>Deletion of PDK1 Caused Cardiac Malmorphogenesis and Heart Defects Due to Profound Protein Phosphorylation Changes Mediated by SHP2</title><title>Journal of cardiovascular translational research</title><addtitle>J. of Cardiovasc. Trans. Res</addtitle><description>Phosphoinositide-dependent protein kinase-1 (PDK
1
), a master kinase and involved in multiple signaling transduction, participates in regulating embryonic cardiac development and postnatal cardiac remodeling. Germline PDK
1
knockout mice displayed no heart development; in this article, we deleted PDK
1
in heart tissue with different cre to characterize the temporospatial features and find the relevance with congenital heart disease(CHD), furthermore to investigate the underlying mechanism. Knocking out PDK
1
with Nkx2.5-cre, the heart showed prominent pulmonic stenosis. Ablated PDK
1
with Mef2c
SHF
-cre, the second heart field (SHF) exhibited severe hypoplasia. And deleted PDK
1
with αMHC-cre, the mice displayed dilated heart disease, protein analysis indicated PI3K and ERK were activated; meanwhile, PDK
1
-AKT-GSK3, and S6K-S6 were disrupted; phosphorylation level of Akt
473
, S6k
421/424
, and Gsk3
α21
enhanced; however, Akt
308
, S6k
389
, and Gsk3
β9
decreased. In mechanism investigation, we found SHP
2
membrane localization and phosphorylation level of SHP2
542
elevated, which suggested SHP
2
likely mediated the disruption.
Graphical abstract</description><subject>Biomedical Engineering and Bioengineering</subject><subject>Biomedicine</subject><subject>Cardiology</subject><subject>Human Genetics</subject><subject>Medicine</subject><subject>Medicine & Public Health</subject><subject>Original Article</subject><issn>1937-5387</issn><issn>1937-5395</issn><fulltext>true</fulltext><rsrctype>article</rsrctype><creationdate>2023</creationdate><recordtype>article</recordtype><recordid>eNp9ULtOwzAUjRBIlMIPMHlkCfgR18mIEqCIVkQCZstxrttUaVzsZMjMj2MaxMh0j3TPQ-dE0TXBtwRjcecJpQseY8piglmK4_EkmpGMiZizjJ_-4VScRxfe7zBeUCzELPoqoIW-sR2yBpXFC0G5GjzU4bi6URqtVbu37rC1G-jANx6prkZLUK5HBRjQvUfFAKi3qHTW2CF8A-ih6VC5tT4I3diqY0K-Vd0GPFpDcO5DRjWit2VJL6Mzo1oPV793Hn08Przny3j1-vSc369izWjSxylwrQnVqa54nYmAEiCK1ZoaoaskNOICFK9TVSlCaMqFqUTFTI0JN5gaNo9uJt-Ds58D-F7uG6-hbVUHdvCSioxyTGiCA5VOVO2s9w6MPLhmr9woCZY_i8tpcRkWl8fF5RhEbBL5QA5NndzZwXWh0n-qb5-UhaE</recordid><startdate>20231001</startdate><enddate>20231001</enddate><creator>Luo, Hongmei</creator><creator>Yang, Zhongzhou</creator><creator>Li, Jie</creator><creator>Jin, Hengwei</creator><creator>Jiang, Mingyang</creator><creator>Shan, Congjia</creator><general>Springer US</general><scope>AAYXX</scope><scope>CITATION</scope><scope>7X8</scope><orcidid>https://orcid.org/0000-0002-6326-2118</orcidid></search><sort><creationdate>20231001</creationdate><title>Deletion of PDK1 Caused Cardiac Malmorphogenesis and Heart Defects Due to Profound Protein Phosphorylation Changes Mediated by SHP2</title><author>Luo, Hongmei ; Yang, Zhongzhou ; Li, Jie ; Jin, Hengwei ; Jiang, Mingyang ; Shan, Congjia</author></sort><facets><frbrtype>5</frbrtype><frbrgroupid>cdi_FETCH-LOGICAL-c324t-8e5cc12c8cb5d9712c4e1a3dc2f7cb406257ea5d8aba112857fb7b3fd015f02f3</frbrgroupid><rsrctype>articles</rsrctype><prefilter>articles</prefilter><language>eng</language><creationdate>2023</creationdate><topic>Biomedical Engineering and Bioengineering</topic><topic>Biomedicine</topic><topic>Cardiology</topic><topic>Human Genetics</topic><topic>Medicine</topic><topic>Medicine & Public Health</topic><topic>Original Article</topic><toplevel>peer_reviewed</toplevel><toplevel>online_resources</toplevel><creatorcontrib>Luo, Hongmei</creatorcontrib><creatorcontrib>Yang, Zhongzhou</creatorcontrib><creatorcontrib>Li, Jie</creatorcontrib><creatorcontrib>Jin, Hengwei</creatorcontrib><creatorcontrib>Jiang, Mingyang</creatorcontrib><creatorcontrib>Shan, Congjia</creatorcontrib><collection>CrossRef</collection><collection>MEDLINE - Academic</collection><jtitle>Journal of cardiovascular translational research</jtitle></facets><delivery><delcategory>Remote Search Resource</delcategory><fulltext>fulltext</fulltext></delivery><addata><au>Luo, Hongmei</au><au>Yang, Zhongzhou</au><au>Li, Jie</au><au>Jin, Hengwei</au><au>Jiang, Mingyang</au><au>Shan, Congjia</au><format>journal</format><genre>article</genre><ristype>JOUR</ristype><atitle>Deletion of PDK1 Caused Cardiac Malmorphogenesis and Heart Defects Due to Profound Protein Phosphorylation Changes Mediated by SHP2</atitle><jtitle>Journal of cardiovascular translational research</jtitle><stitle>J. of Cardiovasc. Trans. Res</stitle><date>2023-10-01</date><risdate>2023</risdate><volume>16</volume><issue>5</issue><spage>1220</spage><epage>1231</epage><pages>1220-1231</pages><issn>1937-5387</issn><eissn>1937-5395</eissn><abstract>Phosphoinositide-dependent protein kinase-1 (PDK
1
), a master kinase and involved in multiple signaling transduction, participates in regulating embryonic cardiac development and postnatal cardiac remodeling. Germline PDK
1
knockout mice displayed no heart development; in this article, we deleted PDK
1
in heart tissue with different cre to characterize the temporospatial features and find the relevance with congenital heart disease(CHD), furthermore to investigate the underlying mechanism. Knocking out PDK
1
with Nkx2.5-cre, the heart showed prominent pulmonic stenosis. Ablated PDK
1
with Mef2c
SHF
-cre, the second heart field (SHF) exhibited severe hypoplasia. And deleted PDK
1
with αMHC-cre, the mice displayed dilated heart disease, protein analysis indicated PI3K and ERK were activated; meanwhile, PDK
1
-AKT-GSK3, and S6K-S6 were disrupted; phosphorylation level of Akt
473
, S6k
421/424
, and Gsk3
α21
enhanced; however, Akt
308
, S6k
389
, and Gsk3
β9
decreased. In mechanism investigation, we found SHP
2
membrane localization and phosphorylation level of SHP2
542
elevated, which suggested SHP
2
likely mediated the disruption.
Graphical abstract</abstract><cop>New York</cop><pub>Springer US</pub><doi>10.1007/s12265-023-10380-y</doi><tpages>12</tpages><orcidid>https://orcid.org/0000-0002-6326-2118</orcidid></addata></record> |
| fulltext | fulltext |
| identifier | ISSN: 1937-5387 |
| ispartof | Journal of cardiovascular translational research, 2023-10, Vol.16 (5), p.1220-1231 |
| issn | 1937-5387 1937-5395 |
| language | eng |
| recordid | cdi_proquest_miscellaneous_2792501240 |
| source | Springer Online Journals Complete |
| subjects | Biomedical Engineering and Bioengineering Biomedicine Cardiology Human Genetics Medicine Medicine & Public Health Original Article |
| title | Deletion of PDK1 Caused Cardiac Malmorphogenesis and Heart Defects Due to Profound Protein Phosphorylation Changes Mediated by SHP2 |
| url | https://sfx.bib-bvb.de/sfx_tum?ctx_ver=Z39.88-2004&ctx_enc=info:ofi/enc:UTF-8&ctx_tim=2024-12-15T13%3A46%3A34IST&url_ver=Z39.88-2004&url_ctx_fmt=infofi/fmt:kev:mtx:ctx&rfr_id=info:sid/primo.exlibrisgroup.com:primo3-Article-proquest_cross&rft_val_fmt=info:ofi/fmt:kev:mtx:journal&rft.genre=article&rft.atitle=Deletion%20of%20PDK1%20Caused%20Cardiac%20Malmorphogenesis%20and%20Heart%20Defects%20Due%20to%20Profound%20Protein%20Phosphorylation%20Changes%20Mediated%20by%20SHP2&rft.jtitle=Journal%20of%20cardiovascular%20translational%20research&rft.au=Luo,%20Hongmei&rft.date=2023-10-01&rft.volume=16&rft.issue=5&rft.spage=1220&rft.epage=1231&rft.pages=1220-1231&rft.issn=1937-5387&rft.eissn=1937-5395&rft_id=info:doi/10.1007/s12265-023-10380-y&rft_dat=%3Cproquest_cross%3E2792501240%3C/proquest_cross%3E%3Curl%3E%3C/url%3E&disable_directlink=true&sfx.directlink=off&sfx.report_link=0&rft_id=info:oai/&rft_pqid=2792501240&rft_id=info:pmid/&rfr_iscdi=true |