Unknown

Dataset Information

0

?2 integrin induces TCR?-Syk-phospholipase C-? phosphorylation and paxillin-dependent granule polarization in human NK cells.


ABSTRACT: Cytotoxic lymphocytes kill target cells through polarized release of the content of lytic granules at the immunological synapse. In human NK cells, signals for granule polarization and for degranulation can be uncoupled: Binding of ?(2) integrin LFA-1 to ICAM is sufficient to induce polarization but not degranulation, whereas CD16 binding to IgG triggers unpolarized degranulation. In this study, we investigated the basis for this difference. IL-2-expanded human NK cells were stimulated by incubation with plate-bound ligands of LFA-1 (ICAM-1) and CD16 (human IgG). Surprisingly, LFA-1 elicited signals similar to those induced by CD16, including tyrosine phosphorylation of the TCR ?-chain, tyrosine kinase Syk, and phospholipase C-?. Whereas CD16 activated Ca(2+) mobilization and LAT phosphorylation, LFA-1 did not, but induced strong Pyk2 and paxillin phosphorylation. LFA-1-dependent granule polarization was blocked by inhibition of Syk, phospholipase C-?, and protein kinase C, as well as by paxillin knockdown. Therefore, common signals triggered by CD16 and LFA-1 bifurcate to provide independent control of Ca(2+)-dependent degranulation and paxillin-dependent granule polarization.

SUBMITTER: March ME 

PROVIDER: S-EPMC3845901 | biostudies-literature | 2011 Mar

REPOSITORIES: biostudies-literature

altmetric image

Publications

β2 integrin induces TCRζ-Syk-phospholipase C-γ phosphorylation and paxillin-dependent granule polarization in human NK cells.

March Michael E ME   Long Eric O EO  

Journal of immunology (Baltimore, Md. : 1950) 20110126 5


Cytotoxic lymphocytes kill target cells through polarized release of the content of lytic granules at the immunological synapse. In human NK cells, signals for granule polarization and for degranulation can be uncoupled: Binding of β(2) integrin LFA-1 to ICAM is sufficient to induce polarization but not degranulation, whereas CD16 binding to IgG triggers unpolarized degranulation. In this study, we investigated the basis for this difference. IL-2-expanded human NK cells were stimulated by incuba  ...[more]

Similar Datasets

| S-EPMC2268177 | biostudies-literature
| S-EPMC10849914 | biostudies-literature
| S-EPMC1221406 | biostudies-other
| S-EPMC2268577 | biostudies-literature
| S-EPMC3399031 | biostudies-other
| S-EPMC2230606 | biostudies-literature
2024-01-31 | GSE229377 | GEO
| S-EPMC2746503 | biostudies-literature
| S-EPMC3867939 | biostudies-literature
| S-EPMC3569986 | biostudies-literature