PXD017088-1

PXD017088 is an original dataset announced via ProteomeXchange.

Title	The integrin linked kinase is required for chemokine-triggered high affinity conformation of the leukocyte β2-integrin LFA-1The integrin linked kinase is required for chemokine-triggered high affinity conformation of the leukocyte β2-integrin LFA-1
Description	Invasion of leukocytes, including neutrophils, in response to injury or infection relies on the orchestrated activation of integrins. The neutrophil integrin lymphocyte function-associated antigen-1 (LFA-1) has been implicated in the regulation of leukocyte adhesion by binding to ICAM-1 expressed on activated endothelial cells. The activation-dependent conformational change of LFA-1 to the high affinity conformation (H+) requires kindlin-3 binding to the tail of the β2-integrin. How the integrin linked kinase (ILK) affects activation of β2-integrins in leukocytes is currently unknown. Here, utilizing in vitro microfluidic adhesion chambers with conformation specific antibodies for neutrophil-like HL-60 cells, we show that knockdown of ILK reduces the conformational change of β2-integrins to the H+ conformation. Consequently, ILK-deficient mice show defects of leukocyte adhesion and recruitment in a chemokine and integrin-dependent cremaster muscle model and in a clinically relevant model of renal-ischemia-reperfusion-injury. Absence of protein kinase C (PKC)-α, which is known to phosphorylate Kindlin-3, reproduces such phenotype in bone marrow chimeric mice. ILK is required for chemokine-induced upregulation of PKC-α activity. Mass spectrometry analysis and western blot analyses revealed a stimulation- and ILK-dependent phosphorylation of kindlin-3 upon activation. Our data thus show that ILK impacts kindlin-3-dependent conformational activation of LFA-1, thus contributing to an inflammatory response.
HostingRepository	PRIDE
AnnounceDate	2020-07-20
AnnouncementXML	Submission_2020-07-20_03:26:11.xml
DigitalObjectIdentifier
ReviewLevel	Peer-reviewed dataset
DatasetOrigin	Original dataset
RepositorySupport	Unsupported dataset by repository
PrimarySubmitter	Hannes Drexler
SpeciesList	scientific name: Homo sapiens (Human); NCBI TaxID: 9606;
ModificationList	phosphorylated residue
Instrument	Q Exactive HF

Revision	Datetime	Status	ChangeLog Entry
0	2020-01-14 01:45:12	ID requested
⏵ 1	2020-07-20 03:26:11	announced
2	2024-10-22 05:09:28	announced	2024-10-22: Updated project metadata.

Dataset with its publication pending

curator keyword: Biomedical

submitter keyword: immunology, neutrophils, integrins, LC-MSMS, mass spectrometry, proteomics, phosphoproteomics

Hannes C. A. Drexler
contact affiliation	Max Planck Institute for Molecular Biomedicine Bioanalytical Mass Spectrometry Röntgenstr. 20 48149 Münster Germany
contact email	hannes.drexler@mpi-muenster.mpg.de
lab head
Hannes Drexler
contact affiliation	Bioanalytical Mass Spectrometry
contact email	hannes.drexler@mpi-muenster.mpg.de
dataset submitter

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PRIDE project URI

• PRIDE
  1. PXD017088
     1. Label: PRIDE project
     2. Name: The integrin linked kinase is required for chemokine-triggered high affinity conformation of the leukocyte β2-integrin LFA-1The integrin linked kinase is required for chemokine-triggered high affinity conformation of the leukocyte β2-integrin LFA-1