Identification of a major determinant for serine-threonine kinase phosphoacceptor specificity.
Eukaryotic protein kinases are generally classified as being either tyrosine or serine-threonine specific. Though not evident from inspection of their primary sequences, many serine-threonine kinases display a significant preference for serine or threonine as the phosphoacceptor residue. Here we sho...
| Үндсэн зохиолчид: | , , , , , , , , , , , , |
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| Формат: | Journal article |
| Хэл сонгох: | English |
| Хэвлэсэн: |
2014
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| _version_ | 1826300951470800896 |
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| author | Chen, C Ha, B Thévenin, A Lou, H Zhang, R Yip, K Peterson, JR Gerstein, M Kim, P Filippakopoulos, P Knapp, S Boggon, T Turk, B |
| author_facet | Chen, C Ha, B Thévenin, A Lou, H Zhang, R Yip, K Peterson, JR Gerstein, M Kim, P Filippakopoulos, P Knapp, S Boggon, T Turk, B |
| author_sort | Chen, C |
| collection | OXFORD |
| description | Eukaryotic protein kinases are generally classified as being either tyrosine or serine-threonine specific. Though not evident from inspection of their primary sequences, many serine-threonine kinases display a significant preference for serine or threonine as the phosphoacceptor residue. Here we show that a residue located in the kinase activation segment, which we term the "DFG+1" residue, acts as a major determinant for serine-threonine phosphorylation site specificity. Mutation of this residue was sufficient to switch the phosphorylation site preference for multiple kinases, including the serine-specific kinase PAK4 and the threonine-specific kinase MST4. Kinetic analysis of peptide substrate phosphorylation and crystal structures of PAK4-peptide complexes suggested that phosphoacceptor residue preference is not mediated by stronger binding of the favored substrate. Rather, favored kinase-phosphoacceptor combinations likely promote a conformation optimal for catalysis. Understanding the rules governing kinase phosphoacceptor preference allows kinases to be classified as serine or threonine specific based on their sequence. |
| first_indexed | 2024-03-07T05:24:58Z |
| format | Journal article |
| id | oxford-uuid:e03ac521-3c27-42ee-ae76-1c7d702e3d2d |
| institution | University of Oxford |
| language | English |
| last_indexed | 2024-03-07T05:24:58Z |
| publishDate | 2014 |
| record_format | dspace |
| spelling | oxford-uuid:e03ac521-3c27-42ee-ae76-1c7d702e3d2d2022-03-27T09:45:37ZIdentification of a major determinant for serine-threonine kinase phosphoacceptor specificity.Journal articlehttp://purl.org/coar/resource_type/c_dcae04bcuuid:e03ac521-3c27-42ee-ae76-1c7d702e3d2dEnglishSymplectic Elements at Oxford2014Chen, CHa, BThévenin, ALou, HZhang, RYip, KPeterson, JRGerstein, MKim, PFilippakopoulos, PKnapp, SBoggon, TTurk, BEukaryotic protein kinases are generally classified as being either tyrosine or serine-threonine specific. Though not evident from inspection of their primary sequences, many serine-threonine kinases display a significant preference for serine or threonine as the phosphoacceptor residue. Here we show that a residue located in the kinase activation segment, which we term the "DFG+1" residue, acts as a major determinant for serine-threonine phosphorylation site specificity. Mutation of this residue was sufficient to switch the phosphorylation site preference for multiple kinases, including the serine-specific kinase PAK4 and the threonine-specific kinase MST4. Kinetic analysis of peptide substrate phosphorylation and crystal structures of PAK4-peptide complexes suggested that phosphoacceptor residue preference is not mediated by stronger binding of the favored substrate. Rather, favored kinase-phosphoacceptor combinations likely promote a conformation optimal for catalysis. Understanding the rules governing kinase phosphoacceptor preference allows kinases to be classified as serine or threonine specific based on their sequence. |
| spellingShingle | Chen, C Ha, B Thévenin, A Lou, H Zhang, R Yip, K Peterson, JR Gerstein, M Kim, P Filippakopoulos, P Knapp, S Boggon, T Turk, B Identification of a major determinant for serine-threonine kinase phosphoacceptor specificity. |
| title | Identification of a major determinant for serine-threonine kinase phosphoacceptor specificity. |
| title_full | Identification of a major determinant for serine-threonine kinase phosphoacceptor specificity. |
| title_fullStr | Identification of a major determinant for serine-threonine kinase phosphoacceptor specificity. |
| title_full_unstemmed | Identification of a major determinant for serine-threonine kinase phosphoacceptor specificity. |
| title_short | Identification of a major determinant for serine-threonine kinase phosphoacceptor specificity. |
| title_sort | identification of a major determinant for serine threonine kinase phosphoacceptor specificity |
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