PKA phosphorylation and 14-3-3 interaction regulate the function of neurofibromatosis type I tumor suppressor, neurofibromin
Neurofibromin, a neurofibromatosis type I (NF1) tumor suppressor gene product, has a domain acting as a GTPase activating protein and functions in part as a negative regulator of Ras. Loss of neurofibromin expression in NF1 patients is associated with elevated Ras activity and increased cell prolife...
Gespeichert in:
| Veröffentlicht in: | FEBS letters 2004-01, Vol.557 (1), p.275-282 |
|---|---|
| Hauptverfasser: | , , , , , , , , |
| Format: | Artikel |
| Sprache: | eng |
| Schlagworte: | |
| Online-Zugang: | Volltext |
| Tags: |
Tag hinzufügen
Keine Tags, Fügen Sie den ersten Tag hinzu!
|
| container_end_page | 282 |
|---|---|
| container_issue | 1 |
| container_start_page | 275 |
| container_title | FEBS letters |
| container_volume | 557 |
| creator | Feng, Liping Yunoue, Shunji Tokuo, Hiroshi Ozawa, Tatsuya Zhang, Dongwei Patrakitkomjorn, Siriporn Ichimura, Toru Saya, Hideyuki Araki, Norie |
| description | Neurofibromin, a neurofibromatosis type I (NF1) tumor suppressor gene product, has a domain acting as a GTPase activating protein and functions in part as a negative regulator of Ras. Loss of neurofibromin expression in NF1 patients is associated with elevated Ras activity and increased cell proliferation. Therefore, regulation of the function of neurofibromin is heavily involved in cell growth and differentiation. In the present study, we identified a novel cellular neurofibromin-associating protein, 14-3-3, which belongs to a highly conserved family of proteins that regulate intracellular signal transduction events in all eukaryotic cells. The interaction of 14-3-3 is mainly directed to the C-terminal domain (CTD) of neurofibromin, and the cAMP-dependent protein kinase (PKA)-dependent phosphorylation clustered on CTD-Ser (2576, 2578, 2580, 2813) and Thr (2556) is required for the interaction. Interestingly, the increased phosphorylation and association of 14-3-3 negatively regulate the function of neurofibromin. These findings indicate that PKA phosphorylation followed by 14-3-3 protein interaction may modulate the biochemical and biological functions of neurofibromin. |
| doi_str_mv | 10.1016/S0014-5793(03)01507-2 |
| format | Article |
| fullrecord | <record><control><sourceid>proquest_cross</sourceid><recordid>TN_cdi_proquest_miscellaneous_17058281</recordid><sourceformat>XML</sourceformat><sourcesystem>PC</sourcesystem><els_id>S0014579303015072</els_id><sourcerecordid>17058281</sourcerecordid><originalsourceid>FETCH-LOGICAL-c5562-f807ac9075cfc38b59b569fd545d1f25f434b07410f925fb2424e99ef74b59543</originalsourceid><addsrcrecordid>eNqNkNtKxDAQhoMouh4eQcmVKFhNmmTbXomKJxQU1OvQphONtE1NWmXBhzfdLuqdQkKYmW_-mfwIbVNySAmdHj0QQnkkkoztEbZPqCBJFC-hCU0TFjE-TZfR5BtZQ-vev5IQpzRbRWuUJ5yylE7Q5_3NCW5frA_Xzaq8M7bBeVPi0Bl0sGk6cLmapx0894EA3L0A1n0zZq3GDfTOalM4W-ed9cbjbtYCvsZdX1uHfd-2Dry37uA3appNtKLzysPW4t1ATxfnj2dX0e3d5fXZyW2khJjGkU5JkquMJEJpxdJCZIWYZroUXJRUx0JzxgsSfkR0FqIi5jGHLAOd8MAKzjbQ7qjbOvvWg-9kbbyCqsobsL2XNCEijVMaQDGCylnvHWjZOlPnbiYpkYPtcm67HDyVJJzBdhmHvp3FgL6oofzpWvgcgKsR-DAVzP6nKi_OT-N5ZSgQNk8Ps45HKQiOvRtw0isDjYLSOFCdLK35Y9svt0Wm9A</addsrcrecordid><sourcetype>Aggregation Database</sourcetype><iscdi>true</iscdi><recordtype>article</recordtype><pqid>17058281</pqid></control><display><type>article</type><title>PKA phosphorylation and 14-3-3 interaction regulate the function of neurofibromatosis type I tumor suppressor, neurofibromin</title><source>MEDLINE</source><source>Wiley Free Content</source><source>ScienceDirect Journals (5 years ago - present)</source><source>EZB-FREE-00999 freely available EZB journals</source><source>Wiley Online Library All Journals</source><source>Alma/SFX Local Collection</source><creator>Feng, Liping ; Yunoue, Shunji ; Tokuo, Hiroshi ; Ozawa, Tatsuya ; Zhang, Dongwei ; Patrakitkomjorn, Siriporn ; Ichimura, Toru ; Saya, Hideyuki ; Araki, Norie</creator><creatorcontrib>Feng, Liping ; Yunoue, Shunji ; Tokuo, Hiroshi ; Ozawa, Tatsuya ; Zhang, Dongwei ; Patrakitkomjorn, Siriporn ; Ichimura, Toru ; Saya, Hideyuki ; Araki, Norie</creatorcontrib><description>Neurofibromin, a neurofibromatosis type I (NF1) tumor suppressor gene product, has a domain acting as a GTPase activating protein and functions in part as a negative regulator of Ras. Loss of neurofibromin expression in NF1 patients is associated with elevated Ras activity and increased cell proliferation. Therefore, regulation of the function of neurofibromin is heavily involved in cell growth and differentiation. In the present study, we identified a novel cellular neurofibromin-associating protein, 14-3-3, which belongs to a highly conserved family of proteins that regulate intracellular signal transduction events in all eukaryotic cells. The interaction of 14-3-3 is mainly directed to the C-terminal domain (CTD) of neurofibromin, and the cAMP-dependent protein kinase (PKA)-dependent phosphorylation clustered on CTD-Ser (2576, 2578, 2580, 2813) and Thr (2556) is required for the interaction. Interestingly, the increased phosphorylation and association of 14-3-3 negatively regulate the function of neurofibromin. These findings indicate that PKA phosphorylation followed by 14-3-3 protein interaction may modulate the biochemical and biological functions of neurofibromin.</description><identifier>ISSN: 0014-5793</identifier><identifier>EISSN: 1873-3468</identifier><identifier>DOI: 10.1016/S0014-5793(03)01507-2</identifier><identifier>PMID: 14741381</identifier><language>eng</language><publisher>England: Elsevier B.V</publisher><subject>14-3-3 protein ; 14-3-3 Proteins ; Alanine ; Amino Acid Sequence ; Amino Acid Substitution ; Animals ; Brain - physiology ; cAMP-dependent protein kinase ; CSRD, cysteine/serine-rich domain ; CTD, C-terminal domain ; Cyclic AMP-Dependent Protein Kinases - genetics ; Cyclic AMP-Dependent Protein Kinases - metabolism ; GAP, GTPase-activity protein ; GRD, GAP-related domain ; GTPase activating protein ; Humans ; Kinetics ; Mutagenesis, Site-Directed ; Neurofibromatosis type I ; Neurofibromin ; Neurofibromin 1 - genetics ; Neurofibromin 1 - metabolism ; NF1, neurofibromatosis type I ; Phosphorylation ; PKA, cAMP-dependent protein kinase ; Plasmids ; Polymerase Chain Reaction ; Rats ; Recombinant Fusion Proteins - metabolism ; Tumor suppressor ; Tyrosine 3-Monooxygenase - genetics ; Tyrosine 3-Monooxygenase - metabolism</subject><ispartof>FEBS letters, 2004-01, Vol.557 (1), p.275-282</ispartof><rights>2003</rights><rights>FEBS Letters 557 (2004) 1873-3468 © 2015 Federation of European Biochemical Societies</rights><lds50>peer_reviewed</lds50><oa>free_for_read</oa><woscitedreferencessubscribed>false</woscitedreferencessubscribed><citedby>FETCH-LOGICAL-c5562-f807ac9075cfc38b59b569fd545d1f25f434b07410f925fb2424e99ef74b59543</citedby><cites>FETCH-LOGICAL-c5562-f807ac9075cfc38b59b569fd545d1f25f434b07410f925fb2424e99ef74b59543</cites></display><links><openurl>$$Topenurl_article</openurl><openurlfulltext>$$Topenurlfull_article</openurlfulltext><thumbnail>$$Tsyndetics_thumb_exl</thumbnail><linktopdf>$$Uhttps://onlinelibrary.wiley.com/doi/pdf/10.1016%2FS0014-5793%2803%2901507-2$$EPDF$$P50$$Gwiley$$H</linktopdf><linktohtml>$$Uhttps://dx.doi.org/10.1016/S0014-5793(03)01507-2$$EHTML$$P50$$Gelsevier$$Hfree_for_read</linktohtml><link.rule.ids>314,780,784,1417,1433,3550,27924,27925,45574,45575,45995,46409,46833</link.rule.ids><backlink>$$Uhttps://www.ncbi.nlm.nih.gov/pubmed/14741381$$D View this record in MEDLINE/PubMed$$Hfree_for_read</backlink></links><search><creatorcontrib>Feng, Liping</creatorcontrib><creatorcontrib>Yunoue, Shunji</creatorcontrib><creatorcontrib>Tokuo, Hiroshi</creatorcontrib><creatorcontrib>Ozawa, Tatsuya</creatorcontrib><creatorcontrib>Zhang, Dongwei</creatorcontrib><creatorcontrib>Patrakitkomjorn, Siriporn</creatorcontrib><creatorcontrib>Ichimura, Toru</creatorcontrib><creatorcontrib>Saya, Hideyuki</creatorcontrib><creatorcontrib>Araki, Norie</creatorcontrib><title>PKA phosphorylation and 14-3-3 interaction regulate the function of neurofibromatosis type I tumor suppressor, neurofibromin</title><title>FEBS letters</title><addtitle>FEBS Lett</addtitle><description>Neurofibromin, a neurofibromatosis type I (NF1) tumor suppressor gene product, has a domain acting as a GTPase activating protein and functions in part as a negative regulator of Ras. Loss of neurofibromin expression in NF1 patients is associated with elevated Ras activity and increased cell proliferation. Therefore, regulation of the function of neurofibromin is heavily involved in cell growth and differentiation. In the present study, we identified a novel cellular neurofibromin-associating protein, 14-3-3, which belongs to a highly conserved family of proteins that regulate intracellular signal transduction events in all eukaryotic cells. The interaction of 14-3-3 is mainly directed to the C-terminal domain (CTD) of neurofibromin, and the cAMP-dependent protein kinase (PKA)-dependent phosphorylation clustered on CTD-Ser (2576, 2578, 2580, 2813) and Thr (2556) is required for the interaction. Interestingly, the increased phosphorylation and association of 14-3-3 negatively regulate the function of neurofibromin. These findings indicate that PKA phosphorylation followed by 14-3-3 protein interaction may modulate the biochemical and biological functions of neurofibromin.</description><subject>14-3-3 protein</subject><subject>14-3-3 Proteins</subject><subject>Alanine</subject><subject>Amino Acid Sequence</subject><subject>Amino Acid Substitution</subject><subject>Animals</subject><subject>Brain - physiology</subject><subject>cAMP-dependent protein kinase</subject><subject>CSRD, cysteine/serine-rich domain</subject><subject>CTD, C-terminal domain</subject><subject>Cyclic AMP-Dependent Protein Kinases - genetics</subject><subject>Cyclic AMP-Dependent Protein Kinases - metabolism</subject><subject>GAP, GTPase-activity protein</subject><subject>GRD, GAP-related domain</subject><subject>GTPase activating protein</subject><subject>Humans</subject><subject>Kinetics</subject><subject>Mutagenesis, Site-Directed</subject><subject>Neurofibromatosis type I</subject><subject>Neurofibromin</subject><subject>Neurofibromin 1 - genetics</subject><subject>Neurofibromin 1 - metabolism</subject><subject>NF1, neurofibromatosis type I</subject><subject>Phosphorylation</subject><subject>PKA, cAMP-dependent protein kinase</subject><subject>Plasmids</subject><subject>Polymerase Chain Reaction</subject><subject>Rats</subject><subject>Recombinant Fusion Proteins - metabolism</subject><subject>Tumor suppressor</subject><subject>Tyrosine 3-Monooxygenase - genetics</subject><subject>Tyrosine 3-Monooxygenase - metabolism</subject><issn>0014-5793</issn><issn>1873-3468</issn><fulltext>true</fulltext><rsrctype>article</rsrctype><creationdate>2004</creationdate><recordtype>article</recordtype><sourceid>EIF</sourceid><recordid>eNqNkNtKxDAQhoMouh4eQcmVKFhNmmTbXomKJxQU1OvQphONtE1NWmXBhzfdLuqdQkKYmW_-mfwIbVNySAmdHj0QQnkkkoztEbZPqCBJFC-hCU0TFjE-TZfR5BtZQ-vev5IQpzRbRWuUJ5yylE7Q5_3NCW5frA_Xzaq8M7bBeVPi0Bl0sGk6cLmapx0894EA3L0A1n0zZq3GDfTOalM4W-ed9cbjbtYCvsZdX1uHfd-2Dry37uA3appNtKLzysPW4t1ATxfnj2dX0e3d5fXZyW2khJjGkU5JkquMJEJpxdJCZIWYZroUXJRUx0JzxgsSfkR0FqIi5jGHLAOd8MAKzjbQ7qjbOvvWg-9kbbyCqsobsL2XNCEijVMaQDGCylnvHWjZOlPnbiYpkYPtcm67HDyVJJzBdhmHvp3FgL6oofzpWvgcgKsR-DAVzP6nKi_OT-N5ZSgQNk8Ps45HKQiOvRtw0isDjYLSOFCdLK35Y9svt0Wm9A</recordid><startdate>20040116</startdate><enddate>20040116</enddate><creator>Feng, Liping</creator><creator>Yunoue, Shunji</creator><creator>Tokuo, Hiroshi</creator><creator>Ozawa, Tatsuya</creator><creator>Zhang, Dongwei</creator><creator>Patrakitkomjorn, Siriporn</creator><creator>Ichimura, Toru</creator><creator>Saya, Hideyuki</creator><creator>Araki, Norie</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>7TK</scope></search><sort><creationdate>20040116</creationdate><title>PKA phosphorylation and 14-3-3 interaction regulate the function of neurofibromatosis type I tumor suppressor, neurofibromin</title><author>Feng, Liping ; Yunoue, Shunji ; Tokuo, Hiroshi ; Ozawa, Tatsuya ; Zhang, Dongwei ; Patrakitkomjorn, Siriporn ; Ichimura, Toru ; Saya, Hideyuki ; Araki, Norie</author></sort><facets><frbrtype>5</frbrtype><frbrgroupid>cdi_FETCH-LOGICAL-c5562-f807ac9075cfc38b59b569fd545d1f25f434b07410f925fb2424e99ef74b59543</frbrgroupid><rsrctype>articles</rsrctype><prefilter>articles</prefilter><language>eng</language><creationdate>2004</creationdate><topic>14-3-3 protein</topic><topic>14-3-3 Proteins</topic><topic>Alanine</topic><topic>Amino Acid Sequence</topic><topic>Amino Acid Substitution</topic><topic>Animals</topic><topic>Brain - physiology</topic><topic>cAMP-dependent protein kinase</topic><topic>CSRD, cysteine/serine-rich domain</topic><topic>CTD, C-terminal domain</topic><topic>Cyclic AMP-Dependent Protein Kinases - genetics</topic><topic>Cyclic AMP-Dependent Protein Kinases - metabolism</topic><topic>GAP, GTPase-activity protein</topic><topic>GRD, GAP-related domain</topic><topic>GTPase activating protein</topic><topic>Humans</topic><topic>Kinetics</topic><topic>Mutagenesis, Site-Directed</topic><topic>Neurofibromatosis type I</topic><topic>Neurofibromin</topic><topic>Neurofibromin 1 - genetics</topic><topic>Neurofibromin 1 - metabolism</topic><topic>NF1, neurofibromatosis type I</topic><topic>Phosphorylation</topic><topic>PKA, cAMP-dependent protein kinase</topic><topic>Plasmids</topic><topic>Polymerase Chain Reaction</topic><topic>Rats</topic><topic>Recombinant Fusion Proteins - metabolism</topic><topic>Tumor suppressor</topic><topic>Tyrosine 3-Monooxygenase - genetics</topic><topic>Tyrosine 3-Monooxygenase - metabolism</topic><toplevel>peer_reviewed</toplevel><toplevel>online_resources</toplevel><creatorcontrib>Feng, Liping</creatorcontrib><creatorcontrib>Yunoue, Shunji</creatorcontrib><creatorcontrib>Tokuo, Hiroshi</creatorcontrib><creatorcontrib>Ozawa, Tatsuya</creatorcontrib><creatorcontrib>Zhang, Dongwei</creatorcontrib><creatorcontrib>Patrakitkomjorn, Siriporn</creatorcontrib><creatorcontrib>Ichimura, Toru</creatorcontrib><creatorcontrib>Saya, Hideyuki</creatorcontrib><creatorcontrib>Araki, Norie</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>Neurosciences Abstracts</collection><jtitle>FEBS letters</jtitle></facets><delivery><delcategory>Remote Search Resource</delcategory><fulltext>fulltext</fulltext></delivery><addata><au>Feng, Liping</au><au>Yunoue, Shunji</au><au>Tokuo, Hiroshi</au><au>Ozawa, Tatsuya</au><au>Zhang, Dongwei</au><au>Patrakitkomjorn, Siriporn</au><au>Ichimura, Toru</au><au>Saya, Hideyuki</au><au>Araki, Norie</au><format>journal</format><genre>article</genre><ristype>JOUR</ristype><atitle>PKA phosphorylation and 14-3-3 interaction regulate the function of neurofibromatosis type I tumor suppressor, neurofibromin</atitle><jtitle>FEBS letters</jtitle><addtitle>FEBS Lett</addtitle><date>2004-01-16</date><risdate>2004</risdate><volume>557</volume><issue>1</issue><spage>275</spage><epage>282</epage><pages>275-282</pages><issn>0014-5793</issn><eissn>1873-3468</eissn><abstract>Neurofibromin, a neurofibromatosis type I (NF1) tumor suppressor gene product, has a domain acting as a GTPase activating protein and functions in part as a negative regulator of Ras. Loss of neurofibromin expression in NF1 patients is associated with elevated Ras activity and increased cell proliferation. Therefore, regulation of the function of neurofibromin is heavily involved in cell growth and differentiation. In the present study, we identified a novel cellular neurofibromin-associating protein, 14-3-3, which belongs to a highly conserved family of proteins that regulate intracellular signal transduction events in all eukaryotic cells. The interaction of 14-3-3 is mainly directed to the C-terminal domain (CTD) of neurofibromin, and the cAMP-dependent protein kinase (PKA)-dependent phosphorylation clustered on CTD-Ser (2576, 2578, 2580, 2813) and Thr (2556) is required for the interaction. Interestingly, the increased phosphorylation and association of 14-3-3 negatively regulate the function of neurofibromin. These findings indicate that PKA phosphorylation followed by 14-3-3 protein interaction may modulate the biochemical and biological functions of neurofibromin.</abstract><cop>England</cop><pub>Elsevier B.V</pub><pmid>14741381</pmid><doi>10.1016/S0014-5793(03)01507-2</doi><tpages>8</tpages><oa>free_for_read</oa></addata></record> |
| fulltext | fulltext |
| identifier | ISSN: 0014-5793 |
| ispartof | FEBS letters, 2004-01, Vol.557 (1), p.275-282 |
| issn | 0014-5793 1873-3468 |
| language | eng |
| recordid | cdi_proquest_miscellaneous_17058281 |
| source | MEDLINE; Wiley Free Content; ScienceDirect Journals (5 years ago - present); EZB-FREE-00999 freely available EZB journals; Wiley Online Library All Journals; Alma/SFX Local Collection |
| subjects | 14-3-3 protein 14-3-3 Proteins Alanine Amino Acid Sequence Amino Acid Substitution Animals Brain - physiology cAMP-dependent protein kinase CSRD, cysteine/serine-rich domain CTD, C-terminal domain Cyclic AMP-Dependent Protein Kinases - genetics Cyclic AMP-Dependent Protein Kinases - metabolism GAP, GTPase-activity protein GRD, GAP-related domain GTPase activating protein Humans Kinetics Mutagenesis, Site-Directed Neurofibromatosis type I Neurofibromin Neurofibromin 1 - genetics Neurofibromin 1 - metabolism NF1, neurofibromatosis type I Phosphorylation PKA, cAMP-dependent protein kinase Plasmids Polymerase Chain Reaction Rats Recombinant Fusion Proteins - metabolism Tumor suppressor Tyrosine 3-Monooxygenase - genetics Tyrosine 3-Monooxygenase - metabolism |
| title | PKA phosphorylation and 14-3-3 interaction regulate the function of neurofibromatosis type I tumor suppressor, neurofibromin |
| url | https://sfx.bib-bvb.de/sfx_tum?ctx_ver=Z39.88-2004&ctx_enc=info:ofi/enc:UTF-8&ctx_tim=2025-01-07T00%3A15%3A06IST&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=PKA%20phosphorylation%20and%2014-3-3%20interaction%20regulate%20the%20function%20of%20neurofibromatosis%20type%20I%20tumor%20suppressor,%20neurofibromin&rft.jtitle=FEBS%20letters&rft.au=Feng,%20Liping&rft.date=2004-01-16&rft.volume=557&rft.issue=1&rft.spage=275&rft.epage=282&rft.pages=275-282&rft.issn=0014-5793&rft.eissn=1873-3468&rft_id=info:doi/10.1016/S0014-5793(03)01507-2&rft_dat=%3Cproquest_cross%3E17058281%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=17058281&rft_id=info:pmid/14741381&rft_els_id=S0014579303015072&rfr_iscdi=true |