An alternative phosphorylation switch in integrin β2 (CD18) tail for Dok1 binding
Integrins are involved in cell migration and adhesion. A large number of proteins interact with the cytoplasmic tails of integrins. Dok1 is a negative regulator of integrin activation and it binds to the phosphorylated membrane proximal NxxY motif in a number of integrin β tails. The β tail of the β...
| Main Authors: | , , , , , |
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| Format: | Journal Article |
| Language: | English |
| Published: |
2015
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| Online Access: | https://hdl.handle.net/10356/93744 http://hdl.handle.net/10220/38329 |
| _version_ | 1826127216085303296 |
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| author | Gupta, Sebanti Chit, Joel Chia-Yeong Feng, Chen Bhunia, Anirban Tan, Suet-Mien Bhattacharjya, Surajit |
| author2 | School of Biological Sciences |
| author_facet | School of Biological Sciences Gupta, Sebanti Chit, Joel Chia-Yeong Feng, Chen Bhunia, Anirban Tan, Suet-Mien Bhattacharjya, Surajit |
| author_sort | Gupta, Sebanti |
| collection | NTU |
| description | Integrins are involved in cell migration and adhesion. A large number of proteins interact with the cytoplasmic tails of integrins. Dok1 is a negative regulator of integrin activation and it binds to the phosphorylated membrane proximal NxxY motif in a number of integrin β tails. The β tail of the β2 integrins contains a non-phosphorylatable NxxF motif. Hence it is unclear how Dok1 associates with the β2 integrins. We showed in this study using NMR and cell based analyses that residues Ser745 and Ser756 in the integrin β2 tail, which are adjacent to the NxxF motif, are required for Dok1 interaction. NMR analyses detected significant chemical shift changes and higher affinity interactions between Dok1 phospho-tyrosine binding (PTB) domain and integrin β2 tail peptide containing pSer756 compared to pSer745. The phosphorylated β2 peptide occupies the canonical ligand binding pocket of Dok1 based on the docked structure of the β2 tail-Dok1 PTB complex. Taken together, our data suggest an alternate phosphorylation switch in β2 integrins that regulates Dok1 binding. This could be important for cells of the immune system and their functions. |
| first_indexed | 2024-10-01T07:05:10Z |
| format | Journal Article |
| id | ntu-10356/93744 |
| institution | Nanyang Technological University |
| language | English |
| last_indexed | 2024-10-01T07:05:10Z |
| publishDate | 2015 |
| record_format | dspace |
| spelling | ntu-10356/937442023-02-28T16:55:43Z An alternative phosphorylation switch in integrin β2 (CD18) tail for Dok1 binding Gupta, Sebanti Chit, Joel Chia-Yeong Feng, Chen Bhunia, Anirban Tan, Suet-Mien Bhattacharjya, Surajit School of Biological Sciences DRNTU::Science::Biological sciences::Microbiology Integrins are involved in cell migration and adhesion. A large number of proteins interact with the cytoplasmic tails of integrins. Dok1 is a negative regulator of integrin activation and it binds to the phosphorylated membrane proximal NxxY motif in a number of integrin β tails. The β tail of the β2 integrins contains a non-phosphorylatable NxxF motif. Hence it is unclear how Dok1 associates with the β2 integrins. We showed in this study using NMR and cell based analyses that residues Ser745 and Ser756 in the integrin β2 tail, which are adjacent to the NxxF motif, are required for Dok1 interaction. NMR analyses detected significant chemical shift changes and higher affinity interactions between Dok1 phospho-tyrosine binding (PTB) domain and integrin β2 tail peptide containing pSer756 compared to pSer745. The phosphorylated β2 peptide occupies the canonical ligand binding pocket of Dok1 based on the docked structure of the β2 tail-Dok1 PTB complex. Taken together, our data suggest an alternate phosphorylation switch in β2 integrins that regulates Dok1 binding. This could be important for cells of the immune system and their functions. Published version 2015-07-14T08:44:29Z 2019-12-06T18:44:44Z 2015-07-14T08:44:29Z 2019-12-06T18:44:44Z 2015 2015 Journal Article Gupta, S., Chit, J. C.-Y., Feng, C., Bhunia, A., Tan, S.-M., & Bhattacharjya, S. (2015). An alternative phosphorylation switch in integrin β2 (CD18) tail for Dok1 binding. Scientific reports, 5, 11630-. 2045-2322 https://hdl.handle.net/10356/93744 http://hdl.handle.net/10220/38329 10.1038/srep11630 26108885 en Scientific reports This work is licensed under a Creative Commons Attribution 4.0 International License. The images or other third party material in this article are included in the article’s Creative Commons license, unless indicated otherwise in the credit line; if the material is not included under the Creative Commons license, users will need to obtain permission from the license holder to reproduce the material. To view a copy of this license, visit http://creativecommons.org/licenses/by/4.0/ 13 p. application/pdf |
| spellingShingle | DRNTU::Science::Biological sciences::Microbiology Gupta, Sebanti Chit, Joel Chia-Yeong Feng, Chen Bhunia, Anirban Tan, Suet-Mien Bhattacharjya, Surajit An alternative phosphorylation switch in integrin β2 (CD18) tail for Dok1 binding |
| title | An alternative phosphorylation switch in integrin β2 (CD18) tail for Dok1 binding |
| title_full | An alternative phosphorylation switch in integrin β2 (CD18) tail for Dok1 binding |
| title_fullStr | An alternative phosphorylation switch in integrin β2 (CD18) tail for Dok1 binding |
| title_full_unstemmed | An alternative phosphorylation switch in integrin β2 (CD18) tail for Dok1 binding |
| title_short | An alternative phosphorylation switch in integrin β2 (CD18) tail for Dok1 binding |
| title_sort | alternative phosphorylation switch in integrin β2 cd18 tail for dok1 binding |
| topic | DRNTU::Science::Biological sciences::Microbiology |
| url | https://hdl.handle.net/10356/93744 http://hdl.handle.net/10220/38329 |
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