Sprouty2 association with B-Raf is regulated by phosphorylation and kinase conformation.
Sprouty2 is a feedback regulator that controls the Ras/Raf/MEK/extracellular signal-regulated kinase mitogen-activated protein kinase (MAPK) pathway at multiple levels, one way being through direct interaction with Raf kinases. Consistent with a role as a tumor suppressor, Sprouty2 expression is oft...
| প্রধান লেখক: | , , , , , |
|---|---|
| বিন্যাস: | Journal article |
| ভাষা: | English |
| প্রকাশিত: |
2009
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| _version_ | 1826272471568875520 |
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| author | Brady, S Coleman, M Munro, J Feller, S Morrice, N Olson, M |
| author_facet | Brady, S Coleman, M Munro, J Feller, S Morrice, N Olson, M |
| author_sort | Brady, S |
| collection | OXFORD |
| description | Sprouty2 is a feedback regulator that controls the Ras/Raf/MEK/extracellular signal-regulated kinase mitogen-activated protein kinase (MAPK) pathway at multiple levels, one way being through direct interaction with Raf kinases. Consistent with a role as a tumor suppressor, Sprouty2 expression is often down-regulated in human cancers. However, Sprouty2 is up-regulated in some cancers, suggesting the existence of posttranscriptional mechanisms that permit evasion of Sprouty2-mediated antitumorigenic properties. We report that MAPK activation induces Sprouty2 phosphorylation on six serine residues, which reduced Sprouty2 association with wild-type B-Raf. Mutation of these six serines to nonphosphorylatable alanines increased the ability of Sprouty2 to inhibit growth factor-induced MAPK activation. Oncogenic B-Raf mutants such as B-Raf V600E did not associate with Sprouty2, but this resistance to Sprouty2 binding was not due to phosphorylation. Instead, the active kinase conformation induced by oncogenic mutation prevents Sprouty2 binding. These results reveal a dual mechanism that affects the Sprouty2/B-Raf interaction: Sprouty phosphorylation and B-Raf conformation. |
| first_indexed | 2024-03-06T22:13:04Z |
| format | Journal article |
| id | oxford-uuid:52758a20-b5bd-4165-b37c-925f55a1cf74 |
| institution | University of Oxford |
| language | English |
| last_indexed | 2024-03-06T22:13:04Z |
| publishDate | 2009 |
| record_format | dspace |
| spelling | oxford-uuid:52758a20-b5bd-4165-b37c-925f55a1cf742022-03-26T16:25:46ZSprouty2 association with B-Raf is regulated by phosphorylation and kinase conformation.Journal articlehttp://purl.org/coar/resource_type/c_dcae04bcuuid:52758a20-b5bd-4165-b37c-925f55a1cf74EnglishSymplectic Elements at Oxford2009Brady, SColeman, MMunro, JFeller, SMorrice, NOlson, MSprouty2 is a feedback regulator that controls the Ras/Raf/MEK/extracellular signal-regulated kinase mitogen-activated protein kinase (MAPK) pathway at multiple levels, one way being through direct interaction with Raf kinases. Consistent with a role as a tumor suppressor, Sprouty2 expression is often down-regulated in human cancers. However, Sprouty2 is up-regulated in some cancers, suggesting the existence of posttranscriptional mechanisms that permit evasion of Sprouty2-mediated antitumorigenic properties. We report that MAPK activation induces Sprouty2 phosphorylation on six serine residues, which reduced Sprouty2 association with wild-type B-Raf. Mutation of these six serines to nonphosphorylatable alanines increased the ability of Sprouty2 to inhibit growth factor-induced MAPK activation. Oncogenic B-Raf mutants such as B-Raf V600E did not associate with Sprouty2, but this resistance to Sprouty2 binding was not due to phosphorylation. Instead, the active kinase conformation induced by oncogenic mutation prevents Sprouty2 binding. These results reveal a dual mechanism that affects the Sprouty2/B-Raf interaction: Sprouty phosphorylation and B-Raf conformation. |
| spellingShingle | Brady, S Coleman, M Munro, J Feller, S Morrice, N Olson, M Sprouty2 association with B-Raf is regulated by phosphorylation and kinase conformation. |
| title | Sprouty2 association with B-Raf is regulated by phosphorylation and kinase conformation. |
| title_full | Sprouty2 association with B-Raf is regulated by phosphorylation and kinase conformation. |
| title_fullStr | Sprouty2 association with B-Raf is regulated by phosphorylation and kinase conformation. |
| title_full_unstemmed | Sprouty2 association with B-Raf is regulated by phosphorylation and kinase conformation. |
| title_short | Sprouty2 association with B-Raf is regulated by phosphorylation and kinase conformation. |
| title_sort | sprouty2 association with b raf is regulated by phosphorylation and kinase conformation |
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