Loading…
mTORC2 Is Involved in the Induction of RSK Phosphorylation by Serum or Nutrient Starvation
Cells adjust to nutrient fluctuations to restore metabolic homeostasis. The mechanistic target of rapamycin (mTOR) complex 2 responds to nutrient levels and growth signals to phosphorylate protein kinases belonging to the AGC (Protein Kinases A,G,C) family such as Akt and PKC. Phosphorylation of the...
Saved in:
Published in: | Cells (Basel, Switzerland) Switzerland), 2020-06, Vol.9 (7), p.1567 |
---|---|
Main Authors: | , , , , , , , , , , |
Format: | Article |
Language: | English |
Subjects: | |
Citations: | Items that this one cites Items that cite this one |
Online Access: | Get full text |
Tags: |
Add Tag
No Tags, Be the first to tag this record!
|
cited_by | cdi_FETCH-LOGICAL-c478t-3e6b10626cadc4aab55fad858fe424d5cce7b461af9d628fca57dc87bfc5d6303 |
---|---|
cites | cdi_FETCH-LOGICAL-c478t-3e6b10626cadc4aab55fad858fe424d5cce7b461af9d628fca57dc87bfc5d6303 |
container_end_page | |
container_issue | 7 |
container_start_page | 1567 |
container_title | Cells (Basel, Switzerland) |
container_volume | 9 |
creator | Chou, Po-Chien Rajput, Swati Zhao, Xiaoyun Patel, Chadni Albaciete, Danielle Oh, Won Jun Daguplo, Heineken Queen Patel, Nikhil Su, Bing Werlen, Guy Jacinto, Estela |
description | Cells adjust to nutrient fluctuations to restore metabolic homeostasis. The mechanistic target of rapamycin (mTOR) complex 2 responds to nutrient levels and growth signals to phosphorylate protein kinases belonging to the AGC (Protein Kinases A,G,C) family such as Akt and PKC. Phosphorylation of these AGC kinases at their conserved hydrophobic motif (HM) site by mTORC2 enhances their activation and mediates the functions of mTORC2 in cell growth and metabolism. Another AGC kinase family member that is known to undergo increased phosphorylation at the homologous HM site (Ser380) is the p90 ribosomal S6 kinase (RSK). Phosphorylation at Ser380 is facilitated by the activation of the mitogen-activated protein kinase/extracellular signal regulated kinase (MAPK/ERK) in response to growth factor stimulation. Here, we demonstrate that optimal phosphorylation of RSK at this site requires an intact mTORC2. We also found that RSK is robustly phosphorylated at Ser380 upon nutrient withdrawal or inhibition of glycolysis, conditions that increase mTORC2 activation. However, pharmacological inhibition of mTOR did not abolish RSK phosphorylation at Ser380, indicating that mTOR catalytic activity is not required for this phosphorylation. Since RSK and SIN1β colocalize at the membrane during serum restimulation and acute glutamine withdrawal, mTORC2 could act as a scaffold to enhance RSK HM site phosphorylation. Among the known RSK substrates, the CCTβ subunit of the chaperonin containing TCP-1 (CCT) complex had defective phosphorylation in the absence of mTORC2. Our findings indicate that the mTORC2-mediated phosphorylation of the RSK HM site could confer RSK substrate specificity and reveal that RSK responds to nutrient fluctuations. |
doi_str_mv | 10.3390/cells9071567 |
format | article |
fullrecord | <record><control><sourceid>proquest_doaj_</sourceid><recordid>TN_cdi_doaj_primary_oai_doaj_org_article_c37c3acda08744d6a7442b784ab14874</recordid><sourceformat>XML</sourceformat><sourcesystem>PC</sourcesystem><doaj_id>oai_doaj_org_article_c37c3acda08744d6a7442b784ab14874</doaj_id><sourcerecordid>2419481223</sourcerecordid><originalsourceid>FETCH-LOGICAL-c478t-3e6b10626cadc4aab55fad858fe424d5cce7b461af9d628fca57dc87bfc5d6303</originalsourceid><addsrcrecordid>eNpdkk1vEzEQhi0EolXpjTOyxIUDAX_be0FCEbQRFUVNuXCxZm1vs9HuOrV3I-Xf4yalSvHBHr_z6JXHMwi9peQT5xX57ELX5YpoKpV-gU4Z0XwmBKleHsUn6DznNSnLUEWJfI1OOFNEEspP0Z_-9vpmzvAi48Wwjd02eNwOeFyFcveTG9s44Njgm-UP_GsV82YV066DvVzv8DKkqccx4Z_TmNowjHg5Qtru82_Qqwa6HM4fzzP0-_u32_nl7Or6YjH_ejVzQptxxoOqKVFMOfBOANRSNuCNNE0QTHjpXNC1UBSayitmGgdSe2d03TjpFSf8DC0Ovj7C2m5S20Pa2Qit3Qsx3VlIY-u6YB3XjoPzQIwWwisoO6u1EVBTUaTi9eXgtZnqPnhXKkrQPTN9nhnalb2LW6sFMWJv8OHRIMX7KeTR9m1-6BIMIU7ZMkErQRXRuqDv_0PXcUpD-aoDZShjvFAfD5RLMecUmqfHUGIfZsAez0DB3x0X8AT_6zj_C1ZqrYg</addsrcrecordid><sourcetype>Open Website</sourcetype><iscdi>true</iscdi><recordtype>article</recordtype><pqid>2419481223</pqid></control><display><type>article</type><title>mTORC2 Is Involved in the Induction of RSK Phosphorylation by Serum or Nutrient Starvation</title><source>Publicly Available Content Database</source><source>PubMed Central(OpenAccess)</source><creator>Chou, Po-Chien ; Rajput, Swati ; Zhao, Xiaoyun ; Patel, Chadni ; Albaciete, Danielle ; Oh, Won Jun ; Daguplo, Heineken Queen ; Patel, Nikhil ; Su, Bing ; Werlen, Guy ; Jacinto, Estela</creator><creatorcontrib>Chou, Po-Chien ; Rajput, Swati ; Zhao, Xiaoyun ; Patel, Chadni ; Albaciete, Danielle ; Oh, Won Jun ; Daguplo, Heineken Queen ; Patel, Nikhil ; Su, Bing ; Werlen, Guy ; Jacinto, Estela</creatorcontrib><description>Cells adjust to nutrient fluctuations to restore metabolic homeostasis. The mechanistic target of rapamycin (mTOR) complex 2 responds to nutrient levels and growth signals to phosphorylate protein kinases belonging to the AGC (Protein Kinases A,G,C) family such as Akt and PKC. Phosphorylation of these AGC kinases at their conserved hydrophobic motif (HM) site by mTORC2 enhances their activation and mediates the functions of mTORC2 in cell growth and metabolism. Another AGC kinase family member that is known to undergo increased phosphorylation at the homologous HM site (Ser380) is the p90 ribosomal S6 kinase (RSK). Phosphorylation at Ser380 is facilitated by the activation of the mitogen-activated protein kinase/extracellular signal regulated kinase (MAPK/ERK) in response to growth factor stimulation. Here, we demonstrate that optimal phosphorylation of RSK at this site requires an intact mTORC2. We also found that RSK is robustly phosphorylated at Ser380 upon nutrient withdrawal or inhibition of glycolysis, conditions that increase mTORC2 activation. However, pharmacological inhibition of mTOR did not abolish RSK phosphorylation at Ser380, indicating that mTOR catalytic activity is not required for this phosphorylation. Since RSK and SIN1β colocalize at the membrane during serum restimulation and acute glutamine withdrawal, mTORC2 could act as a scaffold to enhance RSK HM site phosphorylation. Among the known RSK substrates, the CCTβ subunit of the chaperonin containing TCP-1 (CCT) complex had defective phosphorylation in the absence of mTORC2. Our findings indicate that the mTORC2-mediated phosphorylation of the RSK HM site could confer RSK substrate specificity and reveal that RSK responds to nutrient fluctuations.</description><identifier>ISSN: 2073-4409</identifier><identifier>EISSN: 2073-4409</identifier><identifier>DOI: 10.3390/cells9071567</identifier><identifier>PMID: 32605013</identifier><language>eng</language><publisher>Switzerland: MDPI AG</publisher><subject>AGC kinases ; AKT protein ; Animals ; Antibodies ; Carrier Proteins - genetics ; Carrier Proteins - metabolism ; Cell adhesion & migration ; Cell Membrane - metabolism ; Chaperonins - genetics ; Chaperonins - metabolism ; Extracellular signal-regulated kinase ; Glutamine ; Glycolysis ; Growth factors ; HeLa Cells ; Homeostasis ; Humans ; Hydrophobicity ; Immunoblotting ; Immunoprecipitation ; Kinases ; MAP kinase ; MAPK/ERK ; Mechanistic Target of Rapamycin Complex 2 - genetics ; Mechanistic Target of Rapamycin Complex 2 - metabolism ; Mice ; mTORC2 ; nutrients ; p90 ribosomal s6 kinase ; Phosphorylation ; Protein kinase C ; Protein-serine kinase ; Proteins ; Rapamycin ; Regulation ; Ribosomal protein S6 kinase ; Ribosomal Protein S6 Kinases, 90-kDa - genetics ; Ribosomal Protein S6 Kinases, 90-kDa - metabolism ; RSK ; Substrate specificity ; Thymocytes - metabolism ; TOR protein</subject><ispartof>Cells (Basel, Switzerland), 2020-06, Vol.9 (7), p.1567</ispartof><rights>2020. This work is licensed under http://creativecommons.org/licenses/by/3.0/ (the “License”). Notwithstanding the ProQuest Terms and Conditions, you may use this content in accordance with the terms of the License.</rights><rights>2020 by the authors. 2020</rights><lds50>peer_reviewed</lds50><oa>free_for_read</oa><woscitedreferencessubscribed>false</woscitedreferencessubscribed><citedby>FETCH-LOGICAL-c478t-3e6b10626cadc4aab55fad858fe424d5cce7b461af9d628fca57dc87bfc5d6303</citedby><cites>FETCH-LOGICAL-c478t-3e6b10626cadc4aab55fad858fe424d5cce7b461af9d628fca57dc87bfc5d6303</cites><orcidid>0000-0002-3669-1144 ; 0000-0001-8794-4300 ; 0000-0001-7118-1759</orcidid></display><links><openurl>$$Topenurl_article</openurl><openurlfulltext>$$Topenurlfull_article</openurlfulltext><thumbnail>$$Tsyndetics_thumb_exl</thumbnail><linktopdf>$$Uhttps://www.proquest.com/docview/2419481223/fulltextPDF?pq-origsite=primo$$EPDF$$P50$$Gproquest$$Hfree_for_read</linktopdf><linktohtml>$$Uhttps://www.proquest.com/docview/2419481223?pq-origsite=primo$$EHTML$$P50$$Gproquest$$Hfree_for_read</linktohtml><link.rule.ids>230,314,727,780,784,885,25753,27924,27925,37012,37013,44590,53791,53793,75126</link.rule.ids><backlink>$$Uhttps://www.ncbi.nlm.nih.gov/pubmed/32605013$$D View this record in MEDLINE/PubMed$$Hfree_for_read</backlink></links><search><creatorcontrib>Chou, Po-Chien</creatorcontrib><creatorcontrib>Rajput, Swati</creatorcontrib><creatorcontrib>Zhao, Xiaoyun</creatorcontrib><creatorcontrib>Patel, Chadni</creatorcontrib><creatorcontrib>Albaciete, Danielle</creatorcontrib><creatorcontrib>Oh, Won Jun</creatorcontrib><creatorcontrib>Daguplo, Heineken Queen</creatorcontrib><creatorcontrib>Patel, Nikhil</creatorcontrib><creatorcontrib>Su, Bing</creatorcontrib><creatorcontrib>Werlen, Guy</creatorcontrib><creatorcontrib>Jacinto, Estela</creatorcontrib><title>mTORC2 Is Involved in the Induction of RSK Phosphorylation by Serum or Nutrient Starvation</title><title>Cells (Basel, Switzerland)</title><addtitle>Cells</addtitle><description>Cells adjust to nutrient fluctuations to restore metabolic homeostasis. The mechanistic target of rapamycin (mTOR) complex 2 responds to nutrient levels and growth signals to phosphorylate protein kinases belonging to the AGC (Protein Kinases A,G,C) family such as Akt and PKC. Phosphorylation of these AGC kinases at their conserved hydrophobic motif (HM) site by mTORC2 enhances their activation and mediates the functions of mTORC2 in cell growth and metabolism. Another AGC kinase family member that is known to undergo increased phosphorylation at the homologous HM site (Ser380) is the p90 ribosomal S6 kinase (RSK). Phosphorylation at Ser380 is facilitated by the activation of the mitogen-activated protein kinase/extracellular signal regulated kinase (MAPK/ERK) in response to growth factor stimulation. Here, we demonstrate that optimal phosphorylation of RSK at this site requires an intact mTORC2. We also found that RSK is robustly phosphorylated at Ser380 upon nutrient withdrawal or inhibition of glycolysis, conditions that increase mTORC2 activation. However, pharmacological inhibition of mTOR did not abolish RSK phosphorylation at Ser380, indicating that mTOR catalytic activity is not required for this phosphorylation. Since RSK and SIN1β colocalize at the membrane during serum restimulation and acute glutamine withdrawal, mTORC2 could act as a scaffold to enhance RSK HM site phosphorylation. Among the known RSK substrates, the CCTβ subunit of the chaperonin containing TCP-1 (CCT) complex had defective phosphorylation in the absence of mTORC2. Our findings indicate that the mTORC2-mediated phosphorylation of the RSK HM site could confer RSK substrate specificity and reveal that RSK responds to nutrient fluctuations.</description><subject>AGC kinases</subject><subject>AKT protein</subject><subject>Animals</subject><subject>Antibodies</subject><subject>Carrier Proteins - genetics</subject><subject>Carrier Proteins - metabolism</subject><subject>Cell adhesion & migration</subject><subject>Cell Membrane - metabolism</subject><subject>Chaperonins - genetics</subject><subject>Chaperonins - metabolism</subject><subject>Extracellular signal-regulated kinase</subject><subject>Glutamine</subject><subject>Glycolysis</subject><subject>Growth factors</subject><subject>HeLa Cells</subject><subject>Homeostasis</subject><subject>Humans</subject><subject>Hydrophobicity</subject><subject>Immunoblotting</subject><subject>Immunoprecipitation</subject><subject>Kinases</subject><subject>MAP kinase</subject><subject>MAPK/ERK</subject><subject>Mechanistic Target of Rapamycin Complex 2 - genetics</subject><subject>Mechanistic Target of Rapamycin Complex 2 - metabolism</subject><subject>Mice</subject><subject>mTORC2</subject><subject>nutrients</subject><subject>p90 ribosomal s6 kinase</subject><subject>Phosphorylation</subject><subject>Protein kinase C</subject><subject>Protein-serine kinase</subject><subject>Proteins</subject><subject>Rapamycin</subject><subject>Regulation</subject><subject>Ribosomal protein S6 kinase</subject><subject>Ribosomal Protein S6 Kinases, 90-kDa - genetics</subject><subject>Ribosomal Protein S6 Kinases, 90-kDa - metabolism</subject><subject>RSK</subject><subject>Substrate specificity</subject><subject>Thymocytes - metabolism</subject><subject>TOR protein</subject><issn>2073-4409</issn><issn>2073-4409</issn><fulltext>true</fulltext><rsrctype>article</rsrctype><creationdate>2020</creationdate><recordtype>article</recordtype><sourceid>PIMPY</sourceid><sourceid>DOA</sourceid><recordid>eNpdkk1vEzEQhi0EolXpjTOyxIUDAX_be0FCEbQRFUVNuXCxZm1vs9HuOrV3I-Xf4yalSvHBHr_z6JXHMwi9peQT5xX57ELX5YpoKpV-gU4Z0XwmBKleHsUn6DznNSnLUEWJfI1OOFNEEspP0Z_-9vpmzvAi48Wwjd02eNwOeFyFcveTG9s44Njgm-UP_GsV82YV066DvVzv8DKkqccx4Z_TmNowjHg5Qtru82_Qqwa6HM4fzzP0-_u32_nl7Or6YjH_ejVzQptxxoOqKVFMOfBOANRSNuCNNE0QTHjpXNC1UBSayitmGgdSe2d03TjpFSf8DC0Ovj7C2m5S20Pa2Qit3Qsx3VlIY-u6YB3XjoPzQIwWwisoO6u1EVBTUaTi9eXgtZnqPnhXKkrQPTN9nhnalb2LW6sFMWJv8OHRIMX7KeTR9m1-6BIMIU7ZMkErQRXRuqDv_0PXcUpD-aoDZShjvFAfD5RLMecUmqfHUGIfZsAez0DB3x0X8AT_6zj_C1ZqrYg</recordid><startdate>20200627</startdate><enddate>20200627</enddate><creator>Chou, Po-Chien</creator><creator>Rajput, Swati</creator><creator>Zhao, Xiaoyun</creator><creator>Patel, Chadni</creator><creator>Albaciete, Danielle</creator><creator>Oh, Won Jun</creator><creator>Daguplo, Heineken Queen</creator><creator>Patel, Nikhil</creator><creator>Su, Bing</creator><creator>Werlen, Guy</creator><creator>Jacinto, Estela</creator><general>MDPI AG</general><general>MDPI</general><scope>CGR</scope><scope>CUY</scope><scope>CVF</scope><scope>ECM</scope><scope>EIF</scope><scope>NPM</scope><scope>AAYXX</scope><scope>CITATION</scope><scope>8FD</scope><scope>8FE</scope><scope>8FH</scope><scope>ABUWG</scope><scope>AFKRA</scope><scope>AZQEC</scope><scope>BBNVY</scope><scope>BENPR</scope><scope>BHPHI</scope><scope>CCPQU</scope><scope>DWQXO</scope><scope>FR3</scope><scope>GNUQQ</scope><scope>HCIFZ</scope><scope>LK8</scope><scope>M7P</scope><scope>P64</scope><scope>PIMPY</scope><scope>PQEST</scope><scope>PQQKQ</scope><scope>PQUKI</scope><scope>PRINS</scope><scope>RC3</scope><scope>7X8</scope><scope>5PM</scope><scope>DOA</scope><orcidid>https://orcid.org/0000-0002-3669-1144</orcidid><orcidid>https://orcid.org/0000-0001-8794-4300</orcidid><orcidid>https://orcid.org/0000-0001-7118-1759</orcidid></search><sort><creationdate>20200627</creationdate><title>mTORC2 Is Involved in the Induction of RSK Phosphorylation by Serum or Nutrient Starvation</title><author>Chou, Po-Chien ; Rajput, Swati ; Zhao, Xiaoyun ; Patel, Chadni ; Albaciete, Danielle ; Oh, Won Jun ; Daguplo, Heineken Queen ; Patel, Nikhil ; Su, Bing ; Werlen, Guy ; Jacinto, Estela</author></sort><facets><frbrtype>5</frbrtype><frbrgroupid>cdi_FETCH-LOGICAL-c478t-3e6b10626cadc4aab55fad858fe424d5cce7b461af9d628fca57dc87bfc5d6303</frbrgroupid><rsrctype>articles</rsrctype><prefilter>articles</prefilter><language>eng</language><creationdate>2020</creationdate><topic>AGC kinases</topic><topic>AKT protein</topic><topic>Animals</topic><topic>Antibodies</topic><topic>Carrier Proteins - genetics</topic><topic>Carrier Proteins - metabolism</topic><topic>Cell adhesion & migration</topic><topic>Cell Membrane - metabolism</topic><topic>Chaperonins - genetics</topic><topic>Chaperonins - metabolism</topic><topic>Extracellular signal-regulated kinase</topic><topic>Glutamine</topic><topic>Glycolysis</topic><topic>Growth factors</topic><topic>HeLa Cells</topic><topic>Homeostasis</topic><topic>Humans</topic><topic>Hydrophobicity</topic><topic>Immunoblotting</topic><topic>Immunoprecipitation</topic><topic>Kinases</topic><topic>MAP kinase</topic><topic>MAPK/ERK</topic><topic>Mechanistic Target of Rapamycin Complex 2 - genetics</topic><topic>Mechanistic Target of Rapamycin Complex 2 - metabolism</topic><topic>Mice</topic><topic>mTORC2</topic><topic>nutrients</topic><topic>p90 ribosomal s6 kinase</topic><topic>Phosphorylation</topic><topic>Protein kinase C</topic><topic>Protein-serine kinase</topic><topic>Proteins</topic><topic>Rapamycin</topic><topic>Regulation</topic><topic>Ribosomal protein S6 kinase</topic><topic>Ribosomal Protein S6 Kinases, 90-kDa - genetics</topic><topic>Ribosomal Protein S6 Kinases, 90-kDa - metabolism</topic><topic>RSK</topic><topic>Substrate specificity</topic><topic>Thymocytes - metabolism</topic><topic>TOR protein</topic><toplevel>peer_reviewed</toplevel><toplevel>online_resources</toplevel><creatorcontrib>Chou, Po-Chien</creatorcontrib><creatorcontrib>Rajput, Swati</creatorcontrib><creatorcontrib>Zhao, Xiaoyun</creatorcontrib><creatorcontrib>Patel, Chadni</creatorcontrib><creatorcontrib>Albaciete, Danielle</creatorcontrib><creatorcontrib>Oh, Won Jun</creatorcontrib><creatorcontrib>Daguplo, Heineken Queen</creatorcontrib><creatorcontrib>Patel, Nikhil</creatorcontrib><creatorcontrib>Su, Bing</creatorcontrib><creatorcontrib>Werlen, Guy</creatorcontrib><creatorcontrib>Jacinto, Estela</creatorcontrib><collection>Medline</collection><collection>MEDLINE</collection><collection>MEDLINE (Ovid)</collection><collection>MEDLINE</collection><collection>MEDLINE</collection><collection>PubMed</collection><collection>CrossRef</collection><collection>Technology Research Database</collection><collection>ProQuest SciTech Collection</collection><collection>ProQuest Natural Science Collection</collection><collection>ProQuest Central (Alumni)</collection><collection>ProQuest Central UK/Ireland</collection><collection>ProQuest Central Essentials</collection><collection>Biological Science Collection</collection><collection>ProQuest Central</collection><collection>Natural Science Collection</collection><collection>ProQuest One Community College</collection><collection>ProQuest Central</collection><collection>Engineering Research Database</collection><collection>ProQuest Central Student</collection><collection>SciTech Premium Collection</collection><collection>ProQuest Biological Science Collection</collection><collection>Biological Science Database</collection><collection>Biotechnology and BioEngineering Abstracts</collection><collection>Publicly Available Content Database</collection><collection>ProQuest One Academic Eastern Edition (DO NOT USE)</collection><collection>ProQuest One Academic</collection><collection>ProQuest One Academic UKI Edition</collection><collection>ProQuest Central China</collection><collection>Genetics Abstracts</collection><collection>MEDLINE - Academic</collection><collection>PubMed Central (Full Participant titles)</collection><collection>Directory of Open Access Journals</collection><jtitle>Cells (Basel, Switzerland)</jtitle></facets><delivery><delcategory>Remote Search Resource</delcategory><fulltext>fulltext</fulltext></delivery><addata><au>Chou, Po-Chien</au><au>Rajput, Swati</au><au>Zhao, Xiaoyun</au><au>Patel, Chadni</au><au>Albaciete, Danielle</au><au>Oh, Won Jun</au><au>Daguplo, Heineken Queen</au><au>Patel, Nikhil</au><au>Su, Bing</au><au>Werlen, Guy</au><au>Jacinto, Estela</au><format>journal</format><genre>article</genre><ristype>JOUR</ristype><atitle>mTORC2 Is Involved in the Induction of RSK Phosphorylation by Serum or Nutrient Starvation</atitle><jtitle>Cells (Basel, Switzerland)</jtitle><addtitle>Cells</addtitle><date>2020-06-27</date><risdate>2020</risdate><volume>9</volume><issue>7</issue><spage>1567</spage><pages>1567-</pages><issn>2073-4409</issn><eissn>2073-4409</eissn><abstract>Cells adjust to nutrient fluctuations to restore metabolic homeostasis. The mechanistic target of rapamycin (mTOR) complex 2 responds to nutrient levels and growth signals to phosphorylate protein kinases belonging to the AGC (Protein Kinases A,G,C) family such as Akt and PKC. Phosphorylation of these AGC kinases at their conserved hydrophobic motif (HM) site by mTORC2 enhances their activation and mediates the functions of mTORC2 in cell growth and metabolism. Another AGC kinase family member that is known to undergo increased phosphorylation at the homologous HM site (Ser380) is the p90 ribosomal S6 kinase (RSK). Phosphorylation at Ser380 is facilitated by the activation of the mitogen-activated protein kinase/extracellular signal regulated kinase (MAPK/ERK) in response to growth factor stimulation. Here, we demonstrate that optimal phosphorylation of RSK at this site requires an intact mTORC2. We also found that RSK is robustly phosphorylated at Ser380 upon nutrient withdrawal or inhibition of glycolysis, conditions that increase mTORC2 activation. However, pharmacological inhibition of mTOR did not abolish RSK phosphorylation at Ser380, indicating that mTOR catalytic activity is not required for this phosphorylation. Since RSK and SIN1β colocalize at the membrane during serum restimulation and acute glutamine withdrawal, mTORC2 could act as a scaffold to enhance RSK HM site phosphorylation. Among the known RSK substrates, the CCTβ subunit of the chaperonin containing TCP-1 (CCT) complex had defective phosphorylation in the absence of mTORC2. Our findings indicate that the mTORC2-mediated phosphorylation of the RSK HM site could confer RSK substrate specificity and reveal that RSK responds to nutrient fluctuations.</abstract><cop>Switzerland</cop><pub>MDPI AG</pub><pmid>32605013</pmid><doi>10.3390/cells9071567</doi><orcidid>https://orcid.org/0000-0002-3669-1144</orcidid><orcidid>https://orcid.org/0000-0001-8794-4300</orcidid><orcidid>https://orcid.org/0000-0001-7118-1759</orcidid><oa>free_for_read</oa></addata></record> |
fulltext | fulltext |
identifier | ISSN: 2073-4409 |
ispartof | Cells (Basel, Switzerland), 2020-06, Vol.9 (7), p.1567 |
issn | 2073-4409 2073-4409 |
language | eng |
recordid | cdi_doaj_primary_oai_doaj_org_article_c37c3acda08744d6a7442b784ab14874 |
source | Publicly Available Content Database; PubMed Central(OpenAccess) |
subjects | AGC kinases AKT protein Animals Antibodies Carrier Proteins - genetics Carrier Proteins - metabolism Cell adhesion & migration Cell Membrane - metabolism Chaperonins - genetics Chaperonins - metabolism Extracellular signal-regulated kinase Glutamine Glycolysis Growth factors HeLa Cells Homeostasis Humans Hydrophobicity Immunoblotting Immunoprecipitation Kinases MAP kinase MAPK/ERK Mechanistic Target of Rapamycin Complex 2 - genetics Mechanistic Target of Rapamycin Complex 2 - metabolism Mice mTORC2 nutrients p90 ribosomal s6 kinase Phosphorylation Protein kinase C Protein-serine kinase Proteins Rapamycin Regulation Ribosomal protein S6 kinase Ribosomal Protein S6 Kinases, 90-kDa - genetics Ribosomal Protein S6 Kinases, 90-kDa - metabolism RSK Substrate specificity Thymocytes - metabolism TOR protein |
title | mTORC2 Is Involved in the Induction of RSK Phosphorylation by Serum or Nutrient Starvation |
url | http://sfxeu10.hosted.exlibrisgroup.com/loughborough?ctx_ver=Z39.88-2004&ctx_enc=info:ofi/enc:UTF-8&ctx_tim=2024-12-24T23%3A35%3A30IST&url_ver=Z39.88-2004&url_ctx_fmt=infofi/fmt:kev:mtx:ctx&rfr_id=info:sid/primo.exlibrisgroup.com:primo3-Article-proquest_doaj_&rft_val_fmt=info:ofi/fmt:kev:mtx:journal&rft.genre=article&rft.atitle=mTORC2%20Is%20Involved%20in%20the%20Induction%20of%20RSK%20Phosphorylation%20by%20Serum%20or%20Nutrient%20Starvation&rft.jtitle=Cells%20(Basel,%20Switzerland)&rft.au=Chou,%20Po-Chien&rft.date=2020-06-27&rft.volume=9&rft.issue=7&rft.spage=1567&rft.pages=1567-&rft.issn=2073-4409&rft.eissn=2073-4409&rft_id=info:doi/10.3390/cells9071567&rft_dat=%3Cproquest_doaj_%3E2419481223%3C/proquest_doaj_%3E%3Cgrp_id%3Ecdi_FETCH-LOGICAL-c478t-3e6b10626cadc4aab55fad858fe424d5cce7b461af9d628fca57dc87bfc5d6303%3C/grp_id%3E%3Coa%3E%3C/oa%3E%3Curl%3E%3C/url%3E&rft_id=info:oai/&rft_pqid=2419481223&rft_id=info:pmid/32605013&rfr_iscdi=true |