Inhibition of IgE-mediated mast cell activation by the paired Ig-like receptor PIR-B

Uehara, Takahiro; Bléry, Mathieu; Kang, Dong Won; Chen, Ching-Cheng; Ho, Le Hong; Gartland, G. Larry; Liu, Fu‐Tong; Vivier, Éric; Cooper, Max D.; Kubagawa, Hiromi

doi:10.1172/jci12195

Cited by 26 publications

(24 citation statements)

References 36 publications

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“…By recruiting phosphatase SHP1 and/or SHIP, ITIM-bearing inhibitory receptors suppress cell activation by promoting dephosphorylation reactions. Unlike other myeloid inhibitor receptors such as FcεRIIB [20,21], gp49B1 [22,23], paired Ig-like receptor-B [24,25], and mast cell function-associated antigen [26,27], CD200R lacks an ITIM but contains three tyrosine residues in the cytoplasmic domain. One tyrosine (Y297) is located in an NPxY motif, which may represent a potential PTB domain protein-binding motif.…”

Section: Discussionmentioning

confidence: 99%

Identification of tyrosine residues crucial for CD200R-mediated inhibition of mast cell activation

Zhang¹,

Phillips²

2005

Journal of Leukocyte Biology

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CD200 and its receptor CD200R are type-1 membrane glycoproteins, which contain two immunoglobulin-like domains. Engagement of CD200R by CD200 inhibits activation of myeloid cells. Unlike the majority of immune inhibitory receptors, CD200R does not contain an immunoreceptor tyrosine-based inhibitory motif but contains three tyrosine residues (Y286, Y289, and Y297) in the cytoplasmic domain. Y297 is located in an NPxY motif. Previously, we have shown that engagement of CD200R in mouse mast cells induces its tyrosine phosphorylation and recruitment of inhibitory adaptor proteins Dok1 and Dok2, leading to the inhibition of Ras/mitogen-activated protein kinase activation. In the present study, we examined the roles of these three tyrosines in CD200R-mediated inhibition by site-directed mutagenesis in mouse mast cells. Our data show that Y286 and Y297 are the major phosphorylation sites and are critical for CD200R-mediated inhibition of mast cell activation, and Y289 is dispensable. Our data also suggest that the Src family kinase may mediate the phosphorylation of CD200R and Dok.

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Section: Discussionmentioning

confidence: 99%

Identification of tyrosine residues crucial for CD200R-mediated inhibition of mast cell activation

Zhang¹,

Phillips²

2005

Journal of Leukocyte Biology

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“…These ITIM-containing receptors include FcγRIIb (88), PIR-B (89), gp49B1 (90), myeloid-associated immunoglobulin receptor I (91), mast cell function-associated antigen (92), signal regulator protein α (93), and the recently identified Allergin-1 (94). The mechanisms of FcγRIIb-mediated inhibition of FcϵRI activation have been extensively described.…”

Section: Negative Regulators Of Fcϵri Signalingmentioning

confidence: 99%

Immunoglobulin E Receptor Signaling and Asthma

Wu¹

2011

Journal of Biological Chemistry

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Elevated IgE levels and increased IgE sensitization to allergens are central features of allergic asthma. IgE binds to the high-affinity Fcϵ receptor I (FcϵRI) on mast cells, basophils, and dendritic cells and mediates the activation of these cells upon antigen-induced cross-linking of IgE-bound FcϵRI. FcϵRI activation proceeds through a network of signaling molecules and adaptor proteins and is negatively regulated by a number of cell surface and intracellular proteins. Therapeutic neutralization of serum IgE in moderate-to-severe allergic asthmatics reduces the frequency of asthma exacerbations through a reduction in cell surface FcϵRI expression that results in decreased FcϵRI activation, leading to improved asthma control. Our increasing understanding of IgE receptor signaling may lead to the development of novel therapeutics for the treatment of asthma.

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“…They are not, however, expressed by mature T cells, NK cells, or erythrocytes [9,10]. PIR-A noncovalently associates with the common g-chain of Fc receptor bearing ITAM motifs in the cytoplasmic tail that participates in the cell activating signal pathways [11], while PIR-B possesses functional ITIM motifs in their cytoplasmic tails that transduce negative signals in various cellular events [12][13][14][15]. It has recently been reported that PIR-B-deficient mice were found to be more susceptible to Salmonella infection than WT mice, and that distinct patterns of postinfectional inflammatory lesions, diffuse spreading along the sinusoids, are found in the liver in PIR-Bdeficient mice, while there is nodular restricted localization in WT mice [16].…”

Section: Introductionmentioning

confidence: 99%

The role of dendritic cell subsets in 2,4,6-trinitrobenzene sulfonic acid-induced ileitis

Hoshino

Inaba

Iwai

et al. 2010

Journal of Autoimmunity

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Inhibition of IgE-mediated mast cell activation by the paired Ig-like receptor PIR-B

Cited by 26 publications

References 36 publications

Identification of tyrosine residues crucial for CD200R-mediated inhibition of mast cell activation

Identification of tyrosine residues crucial for CD200R-mediated inhibition of mast cell activation

Immunoglobulin E Receptor Signaling and Asthma

The role of dendritic cell subsets in 2,4,6-trinitrobenzene sulfonic acid-induced ileitis

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