Journal
JOURNAL OF IMMUNOLOGY
Volume 187, Issue 7, Pages 3613-3619Publisher
AMER ASSOC IMMUNOLOGISTS
DOI: 10.4049/jimmunol.1100704
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Funding
- Academy of Finland
- Sigrid Juselius Foundation
- Medicinska Understodsforeningen Liv och Halsa
- Magnus Ehrnrooth Foundation
- Finska Lakaresallskapet
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Adhesion is pivotal for most leukocyte functions, and the beta(2) integrin family of adhesion molecules plays a central role. The integrins need activation to become functional, but the molecular events resulting in adhesion have remained incompletely understood. In human T cells, activation through the TCR results in specific phosphorylation of the T758 on the beta(2) chain of LFA-1. We now show that this phosphorylation leads to downstream binding of 14-3-3 proteins, followed by engagement of the guanine nucleotide exchange factor protein Tiam1 and Rac1 activation. Downregulation of the signaling molecules inhibits LFA-1 activity. Activation by the chemokine stromal cell-derived factor-1 alpha also results in T758 phosphorylation and integrin activation. Thus, TCR and chemokine activation converges on LFA-1 phosphorylation, followed by similar downstream events affecting adhesion. The Journal of Immunology, 2011, 187: 3613-3619.
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