Phosphoproteomic analyses reveal that galectin-1 augments the dynamics of B-cell receptor signaling

Tsai, Chuen-Tinn; Wu, Hsin‐Yi; Su, Tseng-Hsiung; Kuo, Chu-Wei; Huang, Hanwen; Chung, Ching‐Hu; Chen, Chien-Sin; Khoo, Kay‐Hooi; Chen, Yu‐Ju; Lin, Kuo‐I

doi:10.1016/j.jprot.2014.03.031

Cited by 16 publications

(16 citation statements)

References 44 publications

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“…Interestingly, this galectin interacts with the human pre‐B cell receptor via protein–protein recognition, hereby serving as mediator of this receptor's clustering and its activation, initially detecting CD79a tyrosine phosphorylation as a consequence of this receptor's galectin‐triggered activation . Phosphoproteomic analysis of extracts of murine splenic B cells after activation by human galectin‐1 identified alterations of protein phosphorylation via signaling kinases Syk, Btk, and PI3K . In this special case, first insights into galectin‐dependent effects on protein phosphorylation upon cell activation had thus been provided.…”

Section: Discussionmentioning

confidence: 99%

Detection of malignancy‐associated phosphoproteome changes in human colorectal cancer induced by cell surface binding of growth‐inhibitory galectin‐4

et al. 2018

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Emerging evidence on efficient tumor growth regulation by endogenous lectins directs interest to determine on a proof‐of‐principle level the range of information on alterations provided by full‐scale analysis using phosphoproteomics. In our pilot study, we tested galectin‐4 (gal‐4) that is a growth inhibitor for colon cancer cells (CRC), here working with the LS 180 line. In order to cover monitoring of short‐ and long‐term effects stable isotope labeling by amino acids in cell culture‐based quantitative phosphoproteomic analyses were conducted on LS 180 cell preparations collected 1 and 72 h after adding gal‐4 to the culture medium. After short‐term treatment, 981 phosphosites, all of them S/T based, were detected by phosphoproteomics. Changes higher than 1.5‐fold were seen for eight sites in seven proteins. Most affected were the BET1 homolog (BET1), whose level of phosphorylation at S50 was about threefold reduced, and centromere protein F (CENPF), extent of phosphorylation at S3119 doubling in gal‐4‐treated cells. Phosphoproteome analysis after 72 h of treatment revealed marked changes at 33 S/T‐based phosphosites from 29 proteins. Prominent increase of phosphorylation was observed for cofilin‐1 at position S3. Extent of phosphorylation of the glutamine transporter SLC1A5 at position S503 was decreased by a factor of 3. Altered phosphorylation of BET1, CENPF, and cofilin‐1 as well as a significant effect of gal‐4 treatment on glutamine uptake by cells were substantiated by independent methods in the Vaco 432, Colo 205, CX 1, and HCT 116 cell lines. With the example of gal‐4 which functions as a tumor suppressor in CRC cells, we were able to prove that cell surface binding of the lectin not only markedly influences the cell proteome, but also has a bearing on malignancy‐associated intracellular protein phosphorylation. These results underscore the potential of this approach to give further work on elucidating the details of signaling underlying galectin‐triggered growth inhibition a clear direction. © 2018 IUBMB Life, 71(3):364–375, 2019

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Section: Discussionmentioning

confidence: 99%

Detection of malignancy‐associated phosphoproteome changes in human colorectal cancer induced by cell surface binding of growth‐inhibitory galectin‐4

et al. 2018

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“…Notably, the l5 unique region of the pre-BCR represents an unusual example of a nonglycosylated extracellular protein partner of Gal-1, which docks onto a Gal-1 hydrophobic surface adjacent to its CRD and reduces Gal-1 affinity for LacNAc epitopes (21,80). Within the mature B cell compartment, Gal-1 amplifies B cell activation by augmenting the strength of BCR signaling (81,82). In the presence of Gal-1, suboptimal concentrations of anti-IgM triggered full BCR signals in leukemic B cells (81,82), suggesting that Gal-1-glycan interactions act by decreasing the threshold for B cell activation.…”

Section: Taming T Cell and B Cell Functions: Adaptive Immune Programsmentioning

confidence: 99%

“…Within the mature B cell compartment, Gal-1 amplifies B cell activation by augmenting the strength of BCR signaling (81,82). In the presence of Gal-1, suboptimal concentrations of anti-IgM triggered full BCR signals in leukemic B cells (81,82), suggesting that Gal-1-glycan interactions act by decreasing the threshold for B cell activation. Moreover, Gal-1 controls transition of activated B cells toward memory B cell or plasma cell phenotypes (83,84).…”

Section: Taming T Cell and B Cell Functions: Adaptive Immune Programsmentioning

confidence: 99%

Galectin-1: A Jack-of-All-Trades in the Resolution of Acute and Chronic Inflammation

Sundblad

Morosi

Geffner

et al. 2017

The Journal of Immunology

159

136

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Regulatory signals provide negative input to immunological networks promoting resolution of acute and chronic inflammation. Galectin-1 (Gal-1), a member of a family of evolutionarily conserved glycan-binding proteins, displays broad anti-inflammatory and proresolving activities by targeting multiple immune cell types. Within the innate immune compartment, Gal-1 acts as a resolution-associated molecular pattern by counteracting the synthesis of proinflammatory cytokines, inhibiting neutrophil trafficking, targeting eosinophil migration and survival, and suppressing mast cell degranulation. Likewise, this lectin controls T cell and B cell compartments by modulating receptor clustering and signaling, thus serving as a negative-regulatory checkpoint that reprograms cellular activation, differentiation, and survival. In this review, we discuss the central role of Gal-1 in regulatory programs operating during acute inflammation, autoimmune diseases, allergic inflammation, pregnancy, cancer, and infection. Therapeutic strategies aimed at targeting Gal-1-glycan interactions will contribute to overcome cancer immunosuppression and reinforce antimicrobial immunity, whereas stimulation of Gal-1-driven immunoregulatory circuits will help to mitigate exuberant inflammation.

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“…Remarkably, Gal-1 also controls the immunosuppressive activity of Tregs and promotes their differentiation ( 44 – 46 ). Finally, by influencing B-cell development, differentiation, signaling and survival, Gal-1 also controls B-cell function ( 47 – 50 ).…”

Section: Galectins: Key Players In the Inflammatory Responsementioning

confidence: 99%

Galectins in Intestinal Inflammation: Galectin-1 Expression Delineates Response to Treatment in Celiac Disease Patients

et al. 2018

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Galectins, a family of animal lectins characterized by their affinity for N-acetyllactosamine-enriched glycoconjugates, modulate several immune cell processes shaping the course of innate and adaptive immune responses. Through interaction with a wide range of glycosylated receptors bearing complex branched N-glycans and core 2-O-glycans, these endogenous lectins trigger distinct signaling programs thereby controling immune cell activation, differentiation, recruitment and survival. Given the unique features of mucosal inflammation and the differential expression of galectins throughout the gastrointestinal tract, we discuss here key findings on the role of galectins in intestinal inflammation, particularly Crohn’s disease, ulcerative colitis, and celiac disease (CeD) patients, as well as in murine models resembling these inflammatory conditions. In addition, we present new data highlighting the regulated expression of galectin-1 (Gal-1), a proto-type member of the galectin family, during intestinal inflammation in untreated and treated CeD patients. Our results unveil a substantial upregulation of Gal-1 accompanying the anti-inflammatory and tolerogenic response associated with gluten-free diet in CeD patients, suggesting a major role of this lectin in favoring resolution of inflammation and restoration of mucosal homeostasis. Thus, a coordinated network of galectins and their glycosylated ligands, exerting either anti-inflammatory or proinflammatory responses, may influence the interplay between intestinal epithelial cells and the highly specialized gut immune system in physiologic and pathologic settings.

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Phosphoproteomic analyses reveal that galectin-1 augments the dynamics of B-cell receptor signaling

Cited by 16 publications

References 44 publications

Detection of malignancy‐associated phosphoproteome changes in human colorectal cancer induced by cell surface binding of growth‐inhibitory galectin‐4

Detection of malignancy‐associated phosphoproteome changes in human colorectal cancer induced by cell surface binding of growth‐inhibitory galectin‐4

Galectin-1: A Jack-of-All-Trades in the Resolution of Acute and Chronic Inflammation

Galectins in Intestinal Inflammation: Galectin-1 Expression Delineates Response to Treatment in Celiac Disease Patients

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