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- W1844479547 abstract "CD23 is a Type II glycoprotein that exists in both membrane-bound (mbCD23) and soluble (sCD23) forms and functions as the low affinity receptor for IgE. CD23 interacts with a range of proteins to fulfil its function in vivo. Through interactions with its ligands IgE and CD21, CD23 regulates the levels of IgE in serum. Soluble CD23 also interacts with members of the integrin family of membrane receptors. Integrins are heterodimeric transmembrane receptors that participate in bidirectional signalling across membranes and have a critical role in cellular adhesion reactions. CD23 interacts with four integrins, αVβ3 and αVβ5 from the αV integrin family, and αMβ2 and αXβ2, from the β2 family of integrins. Using peptide array technology, we identified set of overlapping peptides derived from the soluble CD23 sequence that interact with integrins expressed on the surface of monocytic cells and with purified αVβ3 and αVβ5 integrins in in vitro Biacore assays. These peptides all contained a common basic tripeptide motif, termed the Arg-Lys-Cys (RKC) motif. Integrins traditionally recognise and bind the Arg-Gly-Asp (RGD) tripeptide in their ligands in a cation-dependent manner. However, the in vitro interaction between RKC-containing peptides and purified integrins was determined to be cation-independent, salt-sensitive and independent of RGD binding. The interaction was blocked by full length CD23. Substitution of the residues in the RKC motif reduced or abolished binding of the peptides to integrins expressed on cells and in vitro, as measured by Biacore analysis, and abolished the competition with CD23. Taken together, these data suggest that the RKC motif is the site in CD23 that is recognised and bound by αVβ3 and αVβ5 integrins. The RKC motif can be considered a novel recognition motif for integrins, as it is cation-independent, and its binding is not blocked by the presence of RGD-containing integrin ligands. Therefore it is likely that the RKC motif interacts with integrins at a site other than that used for RGD-binding, similar to the interactions that have been described for the binding of the HIV Tat protein.The interaction between sCD23 and its integrin receptors is important in the regulation of cytokine production by monocytic cells. Most monocytic cells will express a combination of the different CD23-binding integrins simultaneously and, therefore, the cytokine output of that cell will be the net result of the interaction of CD23 with a combination of integrins. We used monoclonal antibodies to investigate the role of individual integrins in cytokine production. Antibodies were selected to allow comparision of the cytokine response between, a) integrin families, b) integrin subunits, and c) integrin epitopes. The cytokine profile induced by integrin ligation did not differ between the αV and β2 integrin families, although the concentration of cytokines produced varied depending on the heterodimer targeted. However, within a particular family, cytokine production induced by integrin ligation was specific and relied on the recognition of a precise epitope on the integrin. Cytokine production by CD23-binding integrins appears to require the ligation of the α subunit of the integrin heterodimer. We identified an antibody directed against the αVβ3 integrin that induced high levels of cytokine production. Cytokine production following ligation of the integrin with this antibody was dependent on activation of the ERK/MAPK pathway in cells. This production of cytokines and phosphorylation of ERK was enhanced by the addition of macrophage colony stimulating factor (M-CSF) and partially inhibited by an anti-TLR-2 antibody. Chronic stimulation (<3 days) of THP-1 cells with the anti-αVβ3 antibody in the presence of M-CSF led to morphological changes in the cell line associated with the development of a more macrophage-like phenotype and the continued production of cytokines. Analysis of the changes in cell surface marker expression and cytokine profiles suggested that the THP-1 cells had undergone an M2b programme of macrophage activation in response to αVβ3 ligation. Data presented herein reinforce the importance of the role of integrins in the control of adhesion-independent signalling pathways in suspension cells." @default.
- W1844479547 created "2016-06-24" @default.
- W1844479547 creator A5030451379 @default.
- W1844479547 date "2008-01-01" @default.
- W1844479547 modified "2023-09-24" @default.
- W1844479547 title "Integrin-ligand interactions and cytokine production by monocytic cells" @default.
- W1844479547 cites W127545925 @default.
- W1844479547 cites W130820818 @default.
- W1844479547 cites W134178666 @default.
- W1844479547 cites W140814971 @default.
- W1844479547 cites W147592962 @default.
- W1844479547 cites W1480357432 @default.
- W1844479547 cites W1484680841 @default.
- W1844479547 cites W1491336114 @default.
- W1844479547 cites W1508280886 @default.
- W1844479547 cites W1524285426 @default.
- W1844479547 cites W1541817924 @default.
- W1844479547 cites W1542910811 @default.
- W1844479547 cites W1543483858 @default.
- W1844479547 cites W1550039558 @default.
- W1844479547 cites W1551271408 @default.
- W1844479547 cites W1555244835 @default.
- W1844479547 cites W1564434756 @default.
- W1844479547 cites W158225552 @default.
- W1844479547 cites W1590204800 @default.
- W1844479547 cites W1601996378 @default.
- W1844479547 cites W1604781829 @default.
- W1844479547 cites W1604792035 @default.
- W1844479547 cites W1604837267 @default.
- W1844479547 cites W1607041879 @default.
- W1844479547 cites W1610515357 @default.
- W1844479547 cites W1627009127 @default.
- W1844479547 cites W1649140242 @default.
- W1844479547 cites W1689752148 @default.
- W1844479547 cites W1719816833 @default.
- W1844479547 cites W1755490101 @default.
- W1844479547 cites W1838439206 @default.
- W1844479547 cites W1857824984 @default.
- W1844479547 cites W1864154040 @default.
- W1844479547 cites W1872270044 @default.
- W1844479547 cites W1886400351 @default.
- W1844479547 cites W1895807078 @default.
- W1844479547 cites W1923060108 @default.
- W1844479547 cites W1923917571 @default.
- W1844479547 cites W1938388466 @default.
- W1844479547 cites W1941119820 @default.
- W1844479547 cites W1965841931 @default.
- W1844479547 cites W1966734673 @default.
- W1844479547 cites W1967608740 @default.
- W1844479547 cites W1969072247 @default.
- W1844479547 cites W1969740417 @default.
- W1844479547 cites W1970296317 @default.
- W1844479547 cites W1970626272 @default.
- W1844479547 cites W1970923523 @default.
- W1844479547 cites W1973147729 @default.
- W1844479547 cites W1973279572 @default.
- W1844479547 cites W1974043829 @default.
- W1844479547 cites W1974416367 @default.
- W1844479547 cites W1974487938 @default.
- W1844479547 cites W1974674876 @default.
- W1844479547 cites W1975051169 @default.
- W1844479547 cites W1975476602 @default.
- W1844479547 cites W1975815647 @default.
- W1844479547 cites W1977001450 @default.
- W1844479547 cites W1977125553 @default.
- W1844479547 cites W1978201079 @default.
- W1844479547 cites W1980727577 @default.
- W1844479547 cites W1982398946 @default.
- W1844479547 cites W1983466424 @default.
- W1844479547 cites W1984894483 @default.
- W1844479547 cites W1985110057 @default.
- W1844479547 cites W1987241587 @default.
- W1844479547 cites W1987568997 @default.
- W1844479547 cites W1987952124 @default.
- W1844479547 cites W1988028493 @default.
- W1844479547 cites W1988087911 @default.
- W1844479547 cites W1992494265 @default.
- W1844479547 cites W1996348498 @default.
- W1844479547 cites W1997201694 @default.
- W1844479547 cites W1998108337 @default.
- W1844479547 cites W1998301221 @default.
- W1844479547 cites W1998505827 @default.
- W1844479547 cites W1999090056 @default.
- W1844479547 cites W1999250708 @default.
- W1844479547 cites W1999794993 @default.
- W1844479547 cites W2002098156 @default.
- W1844479547 cites W2003366243 @default.
- W1844479547 cites W2003652884 @default.
- W1844479547 cites W2005759392 @default.
- W1844479547 cites W2006513817 @default.
- W1844479547 cites W2006668750 @default.
- W1844479547 cites W2008701946 @default.
- W1844479547 cites W2009636585 @default.
- W1844479547 cites W2010801138 @default.
- W1844479547 cites W2011190969 @default.
- W1844479547 cites W2011217812 @default.
- W1844479547 cites W2012415373 @default.
- W1844479547 cites W2012646902 @default.
- W1844479547 cites W2014776038 @default.
- W1844479547 cites W2015195342 @default.