Phosphorylation of the α-chain in the integrin LFA-1 enables β2-chain phosphorylation and α-actinin binding required for cell adhesion

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Jahan , F , Madhavan , S , Rolova , T , Viazmina , L , Grönholm , M & Gahmberg , C G 2018 , ' Phosphorylation of the α-chain in the integrin LFA-1 enables β2-chain phosphorylation and α-actinin binding required for cell adhesion ' , Journal of Biological Chemistry , vol. 293 , no. 32 , pp. 12318-12330 . https://doi.org/10.1074/jbc.RA118.004318

Title: Phosphorylation of the α-chain in the integrin LFA-1 enables β2-chain phosphorylation and α-actinin binding required for cell adhesion
Author: Jahan, Farhana; Madhavan, Sudarrshan; Rolova, Taisia; Viazmina, Larisa; Grönholm, Mikaela; Gahmberg, Carl G.
Contributor: University of Helsinki, Biosciences
University of Helsinki, Biosciences
University of Helsinki, Biosciences
University of Helsinki, Biosciences
University of Helsinki, Biosciences
Date: 2018-08-10
Language: eng
Number of pages: 13
Belongs to series: Journal of Biological Chemistry
ISSN: 0021-9258
URI: http://hdl.handle.net/10138/303101
Abstract: The integrin leukocyte function-associated antigen-1 (LFA-1) plays a pivotal role in leukocyte adhesion and migration, but the mechanism(s) by which this integrin is regulated has remained incompletely understood. LFA-1 integrin activity requires phosphorylation of its 2-chain and interactions of its cytoplasmic tail with various cellular proteins. The -chain is constitutively phosphorylated and necessary for cellular adhesion, but how the -chain regulates adhesion has remained enigmatic. We now show that substitution of the -chain phosphorylation site (S1140A) in T cells inhibits the phosphorylation of the functionally important Thr-758 in the 2-chain, binding of -actinin and 14-3-3 protein, and expression of an integrin-activating epitope after treatment with the stromal cell-derived factor-1. The presence of this substitution resulted in a loss of cell adhesion and directional cell migration. Moreover, LFA-1 activation through the T-cell receptor in cells expressing the S1140A LFA-1 variant resulted in less Thr-758 phosphorylation, -actinin and talin binding, and cell adhesion. The finding that the LFA-1 -chain regulates adhesion through the -chain via specific phosphorylation at Ser-1140 in the -chain has not been previously reported and emphasizes that both chains are involved in the regulation of LFA-1 integrin activity.
Subject: integrin
phosphorylation
leukocyte
adhesion
talin
14-3-3 protein
filamin
alpha-actinin
FUNCTION-ASSOCIATED ANTIGEN-1
INSIDE-OUT ACTIVATION
CYTOPLASMIC DOMAIN
LEUKOCYTE ADHESION
LIGAND-BINDING
THREONINE PHOSPHORYLATION
T-LYMPHOCYTES
BETA-SUBUNIT
CD18
AFFINITY
1182 Biochemistry, cell and molecular biology
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