Protein tyrosine phosphatase 1B (PTP1B) is dispensable for IgE-mediated cutaneous reaction in vivo

Yang, Ting; Xie, Zhongping; Li, Hua; Yue, Lei; Pang, Zengyuan; MacNeil, Adam J.; Tremblay, Michel L.; Tang, Jintian; Lin, Tong‐Jun

doi:10.1016/j.cellimm.2016.05.005

Cited by 5 publications

(5 citation statements)

References 39 publications

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“…These conflicting outcomes may be because the asthmatic model in the latter study depends on eosinophils and T cells rather than mast cells. In addition, unlike our present results as evaluated by transient by PTP1B knockdown or overexpression, a recent study employing PTP1B knockout has led to the conclusion that PTP1B has a negligible role in mast cell activation 44 . Although the reason for this discrepancy is unclear, similar situations have also been reported for other FcεRI signaling molecules such as Fyn and Lyn 8, 53, 54 .…”

Section: Discussioncontrasting

confidence: 99%

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Sirt1 negatively regulates FcεRI-mediated mast cell activation through AMPK- and PTP1B-dependent processes

Lee

Jin

et al. 2017

Sci Rep

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Sirt1, a key regulator of metabolism and longevity, has recently been implicated in the regulation of allergic reactions, although the underlying mechanism remains unclear. Here we show that Sirt1 negatively regulates FcεRI-stimulated mast cell activation and anaphylaxis through two mutually regulated pathways involving AMP-activated protein kinase (AMPK) and protein tyrosine phosphatase 1B (PTP1B). Mast cell-specific knockout of Sirt1 dampened AMPK-dependent suppression of FcεRI signaling, thereby augmenting mast cell activation both in vitro and in vivo. Sirt1 inhibition of FcεRI signaling also involved an alternative component, PTP1B, which attenuated the inhibitory AMPK pathway and conversely enhanced the stimulatory Syk pathway, uncovering a novel role of this phosphatase. Moreover, a Sirt1 activator resveratrol stimulated the inhibitory AMPK axis, with reciprocal suppression of the stimulatory PTP1B/Syk axis, thus potently inhibiting anaphylaxis. Overall, our results provide a molecular explanation for the beneficial role of Sirt1 in allergy and underscore a potential application of Sirt1 activators as a new class of anti-allergic agents.

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Section: Discussioncontrasting

confidence: 99%

“…While SHP-1 is a well-known protein tyrosine phosphatase that negatively regulates FcεRI signaling 3, 43 , the role of PTP1B in mast cell activation is currently obscure 44 . We found that PTP1B phosphorylation was robustly increased following IgE/Ag stimulation, which was reversed by resveratrol (Fig.…”

Section: Resultsmentioning

confidence: 99%

Sirt1 negatively regulates FcεRI-mediated mast cell activation through AMPK- and PTP1B-dependent processes

Lee

Jin

et al. 2017

Sci Rep

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“…In detail, three overlapping subnetworks were involved in immune activities (i.e., TCR signaling in T cells CD4+ and CD8+ and Signaling mediated by PTP1B ) ( Cho et al. 2013 ; Yang et al. 2016 ), while other two belonged to two P53 protein family pathways (i.e., P53 effectors and P73 network) (supplementary results, Supplementary Material online).…”

Section: Resultsmentioning

confidence: 99%

Evidence of polygenic adaptation to high altitude from Tibetan and Sherpa genomes

Gnecchi‐Ruscone

Abondio

Fanti

et al. 2018

Genome Biology and Evolution

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Although Tibetans and Sherpa present several physiological adjustments evolved to cope with selective pressures imposed by the high-altitude environment, especially hypobaric hypoxia, few selective sweeps at a limited number of hypoxia related genes were confirmed by multiple genomic studies. Nevertheless, variants at these loci were found to be associated only with downregulation of the erythropoietic cascade, which represents an indirect aspect of the considered adaptive phenotype. Accordingly, the genetic basis of Tibetan/Sherpa adaptive traits remains to be fully elucidated, in part due to limitations of selection scans implemented so far and mostly relying on the hard sweep model.In order to overcome this issue, we used whole-genome sequence data and several selection statistics as input for gene network analyses aimed at testing for the occurrence of polygenic adaptation in these high-altitude Himalayan populations. Being able to detect also subtle genomic signatures ascribable to weak positive selection at multiple genes of the same functional subnetwork, this approach allowed us to infer adaptive evolution at loci individually showing small effect sizes, but belonging to highly interconnected biological pathways overall involved in angiogenetic processes.Therefore, these findings pinpointed a series of selective events neglected so far, which likely contributed to the augmented tissue blood perfusion observed in Tibetans and Sherpa, thus uncovering the genetic determinants of a key biological mechanism that underlies their adaptation to high altitude.

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“…Furthermore, other raft proteins identified in this study were also related to the signal transduction pathways in MCs. These proteins included CD45 (receptor-type tyrosine-protein phosphatase C), FcγRII (low affinity immunoglobulin Fc gamma receptor II), MC/stem cell growth factor receptor, IP 3 -receptor, integrins, phospholipid scramblase, serine/threonine-protein phosphatase PP1-alpha, protein-tyrosine phosphatase 1B, IQGAP1, calreticulin, calmodulin, DJ-1, RhoA, Gnai-2, and cdc42 [96,97,98,99,100,101,102].…”

Section: Discussionmentioning

confidence: 99%

Proteomic Analysis of Lipid Rafts from RBL-2H3 Mast Cells

Filho

Jaca

Baeza

et al. 2019

IJMS

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Lipid rafts are highly ordered membrane microdomains enriched in cholesterol, glycosphingolipids, and certain proteins. They are involved in the regulation of cellular processes in diverse cell types, including mast cells (MCs). The MC lipid raft protein composition was assessed using qualitative mass spectrometric characterization of the proteome from detergent-resistant membrane fractions from RBL-2H3 MCs. Using two different post-isolation treatment methods, a total of 949 lipid raft associated proteins were identified. The majority of these MC lipid raft proteins had already been described in the RaftProtV2 database and are among highest cited/experimentally validated lipid raft proteins. Additionally, more than half of the identified proteins had lipid modifications and/or transmembrane domains. Classification of identified proteins into functional categories showed that the proteins were associated with cellular membrane compartments, and with some biological and molecular functions, such as regulation, localization, binding, catalytic activity, and response to stimulus. Furthermore, functional enrichment analysis demonstrated an intimate involvement of identified proteins with various aspects of MC biological processes, especially those related to regulated secretion, organization/stabilization of macromolecules complexes, and signal transduction. This study represents the first comprehensive proteomic profile of MC lipid rafts and provides additional information to elucidate immunoregulatory functions coordinated by raft proteins in MCs.

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Protein tyrosine phosphatase 1B (PTP1B) is dispensable for IgE-mediated cutaneous reaction in vivo

Cited by 5 publications

References 39 publications

Sirt1 negatively regulates FcεRI-mediated mast cell activation through AMPK- and PTP1B-dependent processes

Sirt1 negatively regulates FcεRI-mediated mast cell activation through AMPK- and PTP1B-dependent processes

Evidence of polygenic adaptation to high altitude from Tibetan and Sherpa genomes

Proteomic Analysis of Lipid Rafts from RBL-2H3 Mast Cells

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