Integrin CD11c/CD18 α-Chain Phosphorylation Is Functionally Important

Uotila, Liisa M.; Aatonen, Maria; Gahmberg, Carl G.

doi:10.1074/jbc.c113.497446

Cited by 30 publications

(28 citation statements)

References 41 publications

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“…Phosphorylation of the ␤ 2 chain is needed for the activation of leukocyte integrins, and the signaling cascade downstream of ␤ 2 integrin phosphorylation, leading to rearrangement of the actin cytoskeleton, has been characterized. T cell receptor-induced activation has been found to result in phosphorylated Thr-758 in ␤ 2 , binding of the adaptor protein 14-3-3 and the Rac1 guanine nucleotide exchange factor Tiam1, and, ultimately, to the activation of Rac1, cytoskeleton rearrangements, and integrin clustering (19,21,23). Transfection of a Thr-758-phosphorylated ␤ 2 cytoplasmic peptide was enough to initiate this signaling pathway (19), and we now show that it is sufficient to induce a decrease in VLA-4 ligand binding capacity when transfected into LFA-1-negative cells.…”

Section: Discussionmentioning

confidence: 99%

“…Cell Culture and Transfection-Stable transfectants of the K562 cell line (22) expressing WT CR4 or S1158A-␣ X ␤ 2 (CR4 S/A) or empty plasmid have been described previously (23). HMEC cells were a gift from Antti Vaheri (University of Helsinki, Finland) and have been described previously (24).…”

Section: Methodsmentioning

confidence: 99%

“…For live cell imaging, cells were followed for 10 -120 min, and time lapse movies were taken with the Evos microscope. Adhesion assays of K562 cells to VCAM-1 were performed as described previously (23).…”

Section: Methodsmentioning

confidence: 99%

“…The ␤ 2 integrin CR4 (␣ X ␤ 2 ) is also expressed in leukocytes, and we have shown recently that it is phosphorylated on serine 1158 in the ␣ chain (23). To find out whether the cross-talk is unique to LFA-1, we studied whether CR4 can regulate VLA-4.…”

Section: Strong Adhesion Between Vla-4 and Vcam-1 Causesmentioning

confidence: 99%

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Specific Phosphorylations Transmit Signals from Leukocyte β2 to β1 Integrins and Regulate Adhesion

Uotila

Jahan

Hinojosa

et al. 2014

Journal of Biological Chemistry

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Background:Integrins regulate leukocyte adhesion in a stepwise manner. Results: ␤ 2 Integrins can signal to ␤ 1 integrin very late antigen 4 and inhibit ligand binding. Conclusion: Phosphorylation on both the ␣ and ␤ chains of ␤ 2 integrins are needed, but the signal is transmitted through the ␤ 2 chain, leading to dephosphorylation of ␤ 1 . Significance: Our findings show a mechanism of integrin cross-talk.

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Section: Discussionmentioning

confidence: 99%

Section: Methodsmentioning

confidence: 99%

Section: Methodsmentioning

confidence: 99%

Section: Strong Adhesion Between Vla-4 and Vcam-1 Causesmentioning

confidence: 99%

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Specific Phosphorylations Transmit Signals from Leukocyte β2 to β1 Integrins and Regulate Adhesion

Uotila

Jahan

Hinojosa

et al. 2014

Journal of Biological Chemistry

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“…Opsonization of an antigen by (i)C3b/ C3d results, via CR2, in stimulation of the B cells, which results subsequently in a lowered threshold to produce antibodies [5,93,94]. Besides the well-studied CR2 and C3d interaction, B cells also express CR1 and CR4 which recognize C3b and its degradation product iC3b [95,96]. Synthesis of the separate complement components by B cells has been less well studied.…”

Section: B Cellsmentioning

confidence: 99%

Production of complement components by cells of the immune system

Lubbers

Essen

Kooten

et al. 2017

Clinical and Experimental Immunology

362

281

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SummaryThe complement system is an important part of the innate immune defence. It contributes not only to local inflammation, removal and killing of pathogens, but it also assists in shaping of the adaptive immune response. Besides a role in inflammation, complement is also involved in physiological processes such as waste disposal and developmental programmes. The complement system comprises several soluble and membrane-bound proteins. The bulk of the soluble proteins is produced mainly by the liver. While several complement proteins are produced by a wide variety of cell types, other complement proteins are produced by only a few related cell types. As these data suggest that local production by specific cell types may have specific functions, more detailed studies have been employed recently analysing the local and even intracellular role of these complement proteins.Here we review the current knowledge about extrahepatic production and/ or secretion of complement components. More specifically, we address what is known about complement synthesis by cells of the human immune system.

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Endoplasmic reticulum chaperone gp96 in macrophages is essential for protective immunity during Gram‐negative pneumonia

Anas

Vos

Hoogendijk

et al. 2015

The Journal of Pathology

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Klebsiella pneumoniae is among the most common gram-negative bacteria that cause pneumonia. Gp96 is an endoplasmic reticulum chaperone that is essential for the trafficking and function of Toll-like receptors (TLRs) and integrins. To determine the role of gp96 in myeloid cells in host defence during Klebsiella pneumonia. Mice homozygous for the conditional Hsp90b1 allele encoding gp96 were crossed with mice expressing Cre-recombinase under control of the LysM promoter to generate LysMcre-Hsp90b1-flox mice. LysMcre-Hsp90b1-flox mice showed absence of gp96 protein in macrophages and partial depletion in monocytes and granulocytes. This was accompanied by almost complete absence of TLR2 and TLR4 on macrophages. Likewise, integrin subunits CD11b and CD18 were not detectable on macrophages, while being only slightly reduced on monocytes and granulocytes. Gp96-deficient macrophages did not release pro-inflammatory cytokines in response to Klebsiella and displayed reduced phagocytic capacity independent of CD18. LysMcre-Hsp90b1-flox mice were highly vulnerable to lower airway infection induced by K. pneumoniae, as reflected by an enhanced bacterial growth and a higher mortality rate. The early inflammatory response in Hsp90b1-flox mice was characterized by a strongly impaired recruitment of granulocytes into the lungs, accompanied by an attenuated production of proinflammatory cytokines, while the inflammatory response during late stage pneumonia was not dependent on the presence of gp96. Blocking CD18 did not reproduce the impaired host defence of LysMcre-Hsp90b1-flox mice during Klebsiella pneumonia. These data indicate that macrophage gp96 is essential for protective immunity during gram-negative pneumonia by regulating TLR expression.

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Integrin CD11c/CD18 α-Chain Phosphorylation Is Functionally Important

Cited by 30 publications

References 41 publications

Specific Phosphorylations Transmit Signals from Leukocyte β2 to β1 Integrins and Regulate Adhesion

Specific Phosphorylations Transmit Signals from Leukocyte β2 to β1 Integrins and Regulate Adhesion

Production of complement components by cells of the immune system

Endoplasmic reticulum chaperone gp96 in macrophages is essential for protective immunity during Gram‐negative pneumonia

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