Regulation of eukaryotic initiation factor eIF2B: glycogen synthase kinase-3 phosphorylates a conserved serine which undergoes dephosphorylation in response to insulin
Eukaryotic initiation factor eIF2B catalyses a key regulatory step in mRNA translation. eIF2B and total protein synthesis are acutely activated by insulin, and this requires phosphatidylinositol 3-kinase (PI 3-kinase). The ϵ-subunit of eIF2B is phosphorylated by glycogen synthase kinase-3 (GSK-3), w...
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| Veröffentlicht in: | FEBS letters 1998-01, Vol.421 (2), p.125-130 |
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| creator | Welsh, Gavin I Miller, Christa M Loughlin, A.Jane Price, Nigel T Proud, Christopher G |
| description | Eukaryotic initiation factor eIF2B catalyses a key regulatory step in mRNA translation. eIF2B and total protein synthesis are acutely activated by insulin, and this requires phosphatidylinositol 3-kinase (PI 3-kinase). The ϵ-subunit of eIF2B is phosphorylated by glycogen synthase kinase-3 (GSK-3), which is inactivated by insulin in a PI 3-kinase-dependent manner. Here we identify the phosphorylation site in eIF2Bϵ as Ser
540 and show that treatment of eIF2B with GSK-3 inhibits its activity. Ser
540 is phosphorylated in intact cells and undergoes dephosphorylation in response to insulin. This is blocked by PI 3-kinase inhibitors. Insulin-induced dephosphorylation of this inhibitory site in eIF2B seems likely to be important in the overall activation of translation by this hormone. |
| doi_str_mv | 10.1016/S0014-5793(97)01548-2 |
| format | Article |
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540 and show that treatment of eIF2B with GSK-3 inhibits its activity. Ser
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540 and show that treatment of eIF2B with GSK-3 inhibits its activity. Ser
540 is phosphorylated in intact cells and undergoes dephosphorylation in response to insulin. This is blocked by PI 3-kinase inhibitors. Insulin-induced dephosphorylation of this inhibitory site in eIF2B seems likely to be important in the overall activation of translation by this hormone.</description><subject>Amino Acid Sequence</subject><subject>Animals</subject><subject>Binding Sites</subject><subject>Calcium-Calmodulin-Dependent Protein Kinases - metabolism</subject><subject>CHO Cells</subject><subject>Conserved Sequence</subject><subject>Cricetinae</subject><subject>Eukaryotic initiation factor</subject><subject>Eukaryotic Initiation Factor-2 - genetics</subject><subject>Eukaryotic Initiation Factor-2 - metabolism</subject><subject>Glycogen Synthase Kinase 3</subject><subject>Glycogen Synthase Kinases</subject><subject>Insulin</subject><subject>Insulin - metabolism</subject><subject>Insulin - pharmacology</subject><subject>Molecular Sequence Data</subject><subject>Phosphorylation</subject><subject>Rabbits</subject><subject>Serine - metabolism</subject><issn>0014-5793</issn><issn>1873-3468</issn><fulltext>true</fulltext><rsrctype>article</rsrctype><creationdate>1998</creationdate><recordtype>article</recordtype><sourceid>EIF</sourceid><recordid>eNqNUUtv1DAQthCoLIWfUMknBIeAH_E65oJo1W0rVULicba89mTXNGsvdtIqv4i_WWezqrjBwRrNfI-x5kPojJIPlNDlx--E0LoSUvF3Sr4nVNRNxZ6hBW0kr3i9bJ6jxRPlJXqV8y9S-oaqE3SiCs4UW6A_32AzdKb3MeDYYhjuTBpj7y32wfd-Blpj-5gw3KzY-Se86UYbNxBwHkO_NRnwnQ-lVBzvtzGXl8biCBkbbGPIkO7B4VJ8APyw9XaLh-AgbWKhOPhbMy3zASfI-0mI-1jaPHQ-vEYvWtNleHOsp-jn6vLHxXV1-_Xq5uLLbWVFzVklCTfUrTll61aYRgnHVGvXBniZCzCGC8EoJ4zXtVxyIYmT3BluLW-4U5aforez7z7F3wPkXu98ttB1JkAcspZq2QjGSCGKmWhTzDlBq_fJ78rxNCV6CkgfAtLT9bWS-hCQZkV3dlwwrHfgnlTHRAp-PeMPvoPx_0z16vKcHZAJUPIwnqw-z1ZQDnbvIelsPQQLziewvXbR_-Ozj5dtuG0</recordid><startdate>19980109</startdate><enddate>19980109</enddate><creator>Welsh, Gavin I</creator><creator>Miller, Christa M</creator><creator>Loughlin, A.Jane</creator><creator>Price, Nigel T</creator><creator>Proud, Christopher G</creator><general>Elsevier B.V</general><scope>6I.</scope><scope>AAFTH</scope><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>7X8</scope></search><sort><creationdate>19980109</creationdate><title>Regulation of eukaryotic initiation factor eIF2B: glycogen synthase kinase-3 phosphorylates a conserved serine which undergoes dephosphorylation in response to insulin</title><author>Welsh, Gavin I ; Miller, Christa M ; Loughlin, A.Jane ; Price, Nigel T ; Proud, Christopher G</author></sort><facets><frbrtype>5</frbrtype><frbrgroupid>cdi_FETCH-LOGICAL-c5432-703a1db312bf5a895d29fcbae33a15eaa35521302344763570d73da3cc383d9c3</frbrgroupid><rsrctype>articles</rsrctype><prefilter>articles</prefilter><language>eng</language><creationdate>1998</creationdate><topic>Amino Acid Sequence</topic><topic>Animals</topic><topic>Binding Sites</topic><topic>Calcium-Calmodulin-Dependent Protein Kinases - metabolism</topic><topic>CHO Cells</topic><topic>Conserved Sequence</topic><topic>Cricetinae</topic><topic>Eukaryotic initiation factor</topic><topic>Eukaryotic Initiation Factor-2 - genetics</topic><topic>Eukaryotic Initiation Factor-2 - metabolism</topic><topic>Glycogen Synthase Kinase 3</topic><topic>Glycogen Synthase Kinases</topic><topic>Insulin</topic><topic>Insulin - metabolism</topic><topic>Insulin - pharmacology</topic><topic>Molecular Sequence Data</topic><topic>Phosphorylation</topic><topic>Rabbits</topic><topic>Serine - metabolism</topic><toplevel>peer_reviewed</toplevel><toplevel>online_resources</toplevel><creatorcontrib>Welsh, Gavin I</creatorcontrib><creatorcontrib>Miller, Christa M</creatorcontrib><creatorcontrib>Loughlin, A.Jane</creatorcontrib><creatorcontrib>Price, Nigel T</creatorcontrib><creatorcontrib>Proud, Christopher G</creatorcontrib><collection>ScienceDirect Open Access Titles</collection><collection>Elsevier:ScienceDirect:Open Access</collection><collection>Medline</collection><collection>MEDLINE</collection><collection>MEDLINE (Ovid)</collection><collection>MEDLINE</collection><collection>MEDLINE</collection><collection>PubMed</collection><collection>CrossRef</collection><collection>MEDLINE - Academic</collection><jtitle>FEBS letters</jtitle></facets><delivery><delcategory>Remote Search Resource</delcategory><fulltext>fulltext</fulltext></delivery><addata><au>Welsh, Gavin I</au><au>Miller, Christa M</au><au>Loughlin, A.Jane</au><au>Price, Nigel T</au><au>Proud, Christopher G</au><format>journal</format><genre>article</genre><ristype>JOUR</ristype><atitle>Regulation of eukaryotic initiation factor eIF2B: glycogen synthase kinase-3 phosphorylates a conserved serine which undergoes dephosphorylation in response to insulin</atitle><jtitle>FEBS letters</jtitle><addtitle>FEBS Lett</addtitle><date>1998-01-09</date><risdate>1998</risdate><volume>421</volume><issue>2</issue><spage>125</spage><epage>130</epage><pages>125-130</pages><issn>0014-5793</issn><eissn>1873-3468</eissn><abstract>Eukaryotic initiation factor eIF2B catalyses a key regulatory step in mRNA translation. eIF2B and total protein synthesis are acutely activated by insulin, and this requires phosphatidylinositol 3-kinase (PI 3-kinase). The ϵ-subunit of eIF2B is phosphorylated by glycogen synthase kinase-3 (GSK-3), which is inactivated by insulin in a PI 3-kinase-dependent manner. Here we identify the phosphorylation site in eIF2Bϵ as Ser
540 and show that treatment of eIF2B with GSK-3 inhibits its activity. Ser
540 is phosphorylated in intact cells and undergoes dephosphorylation in response to insulin. This is blocked by PI 3-kinase inhibitors. Insulin-induced dephosphorylation of this inhibitory site in eIF2B seems likely to be important in the overall activation of translation by this hormone.</abstract><cop>England</cop><pub>Elsevier B.V</pub><pmid>9468292</pmid><doi>10.1016/S0014-5793(97)01548-2</doi><tpages>6</tpages><oa>free_for_read</oa></addata></record> |
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| ispartof | FEBS letters, 1998-01, Vol.421 (2), p.125-130 |
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| source | MEDLINE; Wiley Online Library Journals Frontfile Complete; Elsevier ScienceDirect Journals; Wiley Online Library Free Content; Elektronische Zeitschriftenbibliothek - Frei zugängliche E-Journals; Alma/SFX Local Collection |
| subjects | Amino Acid Sequence Animals Binding Sites Calcium-Calmodulin-Dependent Protein Kinases - metabolism CHO Cells Conserved Sequence Cricetinae Eukaryotic initiation factor Eukaryotic Initiation Factor-2 - genetics Eukaryotic Initiation Factor-2 - metabolism Glycogen Synthase Kinase 3 Glycogen Synthase Kinases Insulin Insulin - metabolism Insulin - pharmacology Molecular Sequence Data Phosphorylation Rabbits Serine - metabolism |
| title | Regulation of eukaryotic initiation factor eIF2B: glycogen synthase kinase-3 phosphorylates a conserved serine which undergoes dephosphorylation in response to insulin |
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