Differential activation of LFA-1 and Mac-1 ligand binding domains

Walters, Susannah E.; Tang, Renhong; Cheng, Ming Shien; Tan, Suet-Mien; Law, S.K. Alex

doi:10.1016/j.bbrc.2005.08.269

Cited by 7 publications

(5 citation statements)

References 29 publications

Supporting

Mentioning

Contrasting

Order By: Relevance

“…The hybridomas of mAb KIM185 (specific for integrin β2 and activating), 18 mAb KIM127 (specific for integrin β2; reporter mAb for an extended β2 integrin), 21,22 and IB4 (specific for the heterodimeric form of β2 integrins) 19,44,45 (c), denatured BSA was used as ligand, as described previously. 36 In all experiments, the β2 integrin heterodimer-specific and function-blocking mAb IB4 was included to demonstrate β2-integrin-mediated binding specificity.…”

Section: Antibodies and Reagentsmentioning

confidence: 99%

A Transmembrane Polar Interaction Is Involved in the Functional Regulation of Integrin αLβ2

Vararattanavech

Chng

Parthasarathy

et al. 2010

Journal of Molecular Biology

Self Cite

View full text Add to dashboard Cite

Section: Antibodies and Reagentsmentioning

confidence: 99%

A Transmembrane Polar Interaction Is Involved in the Functional Regulation of Integrin αLβ2

Vararattanavech

Chng

Parthasarathy

et al. 2010

Journal of Molecular Biology

Self Cite

View full text Add to dashboard Cite

“…The logical expected impact of cytohesin-1 inhibition or silencing was inhibition of Mac-1 activation, as cytohesin-1 interacts with the ␤ 2 -chain shared by all of the ␤ 2 integrins. LFA-1 and Mac-1 present several structural differences, allowing differential regulation and functioning via the cytoplasmic domains of their respective ␣-chain [60,61]. In fact, LFA-1 molecules are implicated in slow rolling and arrests, whereas Mac-1 maintains stable adhesion over minutes of applied shear flow [62] and is required for crawling [43].…”

Section: Figure 8 Effect Of Cytohesin-1 Inhibition On Cell Surface Ementioning

confidence: 99%

Cytohesin-1 regulates fMLF-mediated activation and functions of the β2 integrin Mac-1 in human neutrophils

Azreq

Garceau

Bourgoin

2011

Journal of Leukocyte Biology

View full text Add to dashboard Cite

The nucleotide exchange factor cytohesin-1 was previously reported to interact with the cytoplasmic domains of the integrin β-chain common to all β(2) integrins such as LFA-1 and Mac-1. We show here that cytohesin-1, which contributes to fMLF-induced functional responses in PMNs through activation of Arf6, restrains the activation of the β(2) integrin Mac-1 (αMβ(2)) in PMNs or dcAMP-differentiated PLB-985 cells. We found that the cytohesin-1 inhibitor SecinH3 or siRNA increased cell adhesion to immobilized fibrinogen and fMLF-mediated conformational changes of Mac-1, monitored using mAb CBRM1/5, specific for the activation epitope of the αM subunit. In contrast, PLB-985 cells overexpressing cytohesin-1 showed little adhesion to fibrinogen. The use of SecinH3 and siRNA also revealed that interference with cytohesin-1 signaling also enhanced phagocytosis of zymosan particles and chemotaxis toward fMLF in transwell migration assays. These increments of phagocytosis and chemotaxis in cells treated with SecinH3 and cytohesin-1 siRNA were reversed by a blocking mAb to the integrin-αM subunit. We provide evidence for increased polymerized cortical actin in cells treated with SecinH3 and that altered signaling through cytohesin-1 increased cell surface expression of FPRL-1 and impairs the late calcium mobilization response elicited by fMLF. The data provide evidence that stimulation with fMLF initiates a signaling cascade that restrains Mac-1 activation in PMNs. Such crosstalk between FPRL-1 and Mac-1 involves cytohesin-1. We suggest that cytohesin-1 may coordinate activation of the β(2) integrins to regulate PMN adhesion, phagocytosis, and chemotaxis.

show abstract

“…The last helix in the open conformer is shifted downward compared with the closed conformer ( Figure 4F). Apparently, this conform-ational change also involves disrupting the interaction between an isoleucine residue in the last helix and a hydrophobic pocket in the I domain known as the SILEN (socket for isoleucine; Figure 4F) [7,[65][66][67][68][69]. It has been shown that locking the last helix of the I domain in the closed or open conformation using engineered disulfide bonds induces low or high ligand-binding affinity respectively in both the integrin αMβ2 and its isolated I domain [64].…”

Section: Introductionmentioning

confidence: 99%

“…The positions of the co-ordinating residues in the α I domain MIDAS are also different between the two conformers ( Figure 4G). However, SILEN may not serve as the primary allosteric switch in all I domains because a mutation that disrupted SILEN in the integrin αM I domain, but not the αL I domain, was activating [69]. Thus the downward movement of the last helix in the α I domain regulates the ligand-binding affinity of its MIDAS.…”

Section: Introductionmentioning

confidence: 99%

The leucocyte β2 (CD18) integrins: the structure, functional regulation and signalling properties

2012

Self Cite

View full text Add to dashboard Cite

Leucocytes are highly motile cells. Their ability to migrate into tissues and organs is dependent on cell adhesion molecules. The integrins are a family of heterodimeric transmembrane cell adhesion molecules that are also signalling receptors. They are involved in many biological processes, including the development of metazoans, immunity, haemostasis, wound healing and cell survival, proliferation and differentiation. The leucocyte-restricted β2 integrins comprise four members, namely αLβ2, αMβ2, αXβ2 and αDβ2, which are required for a functional immune system. In this paper, the structure, functional regulation and signalling properties of these integrins are reviewed.

show abstract

Differential activation of LFA-1 and Mac-1 ligand binding domains

Cited by 7 publications

References 29 publications

A Transmembrane Polar Interaction Is Involved in the Functional Regulation of Integrin αLβ2

A Transmembrane Polar Interaction Is Involved in the Functional Regulation of Integrin αLβ2

Cytohesin-1 regulates fMLF-mediated activation and functions of the β2 integrin Mac-1 in human neutrophils

The leucocyte β2 (CD18) integrins: the structure, functional regulation and signalling properties

Contact Info

Product

Resources

About