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...

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Main Authors: Gupta, Sebanti, Chit, Joel Chia-Yeong, Feng, Chen, Bhunia, Anirban, Tan, Suet-Mien, Bhattacharjya, Surajit
Other Authors: School of Biological Sciences
Format: Article
Language:English
Published: 2015
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Online Access:https://hdl.handle.net/10356/93744
http://hdl.handle.net/10220/38329
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Institution: Nanyang Technological University
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spelling sg-ntu-dr.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
institution Nanyang Technological University
building NTU Library
continent Asia
country Singapore
Singapore
content_provider NTU Library
collection DR-NTU
language English
topic DRNTU::Science::Biological sciences::Microbiology
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
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.
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
format Article
author Gupta, Sebanti
Chit, Joel Chia-Yeong
Feng, Chen
Bhunia, Anirban
Tan, Suet-Mien
Bhattacharjya, Surajit
author_sort Gupta, Sebanti
title 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_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_sort alternative phosphorylation switch in integrin β2 (cd18) tail for dok1 binding
publishDate 2015
url https://hdl.handle.net/10356/93744
http://hdl.handle.net/10220/38329
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