Transglutaminase-2 Interaction with Heparin

Lortat‐Jacob, Hugues; Burhan, Izhar; Scarpellini, Alessandra; Thomas, Aline; Imberty, Anne; Vivès, Romain R.; Johnson, Timothy S.; Gutiérrez, Aldo; Verderio, Elisabetta

doi:10.1074/jbc.m111.337089

Cited by 56 publications

(65 citation statements)

References 51 publications

(87 reference statements)

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“…It is known that residues proximal to the GAG-binding domains can influence the strength of GAG-protein interactions (Hileman et al, 1998;Lortat-Jacob et al, 2012). The stronger heparin-binding activity detected in BFPP-associated point mutants (R38W, Y88C and C91S) seems to reinforce this notion (Fig.…”

Section: -Test) (E-g)mentioning

confidence: 64%

“…As collagen III and TG2 themselves are also heparin-binding proteins (Lortat-Jacob et al, 2012;San Antonio et al, 1994), the overlapping and close proximity of the heparininteracting domains with the collagen-III-and TG2-binding sites strongly suggest that heparin might modulate the interaction of GPR56 with its protein ligand(s) (Fig. S4).…”

Section: -Test) (E-g)mentioning

confidence: 99%

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Heparin interacts with the adhesion GPCR GPR56, reduces receptor shedding, and promotes cell adhesion and motility

Chiang

Chang

Huang

et al. 2016

Journal of Cell Science

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GPR56 is an adhesion-class G-protein-coupled receptor responsible for bilateral frontoparietal polymicrogyria (BFPP), a severe disorder of cortical formation. Additionally, GPR56 is involved in biological processes as diverse as hematopoietic stem cell generation and maintenance, myoblast fusion, muscle hypertrophy, immunoregulation and tumorigenesis. Collagen III and tissue transglutaminase 2 (TG2) have been revealed as the matricellular ligands of GPR56 involved in BFPP and melanoma development, respectively. In this study, we identify heparin as a glycosaminoglycan interacting partner of GPR56. Analyses of truncated and mutant GPR56 proteins reveal two basicresidue-rich clusters, R , as the major heparin-interacting motifs that overlap partially with the collagen III-and TG2-binding sites. Interestingly, the GPR56-heparin interaction is modulated by collagen III but not TG2, even though both ligands are also heparin-binding proteins. Finally, we show that the interaction with heparin reduces GPR56 receptor shedding, and enhances cell adhesion and motility. These results provide novel insights into the interaction of GPR56 with its multiple endogenous ligands and have functional implications in diseases such as BFPP and cancer.

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Section: -Test) (E-g)mentioning

confidence: 64%

Section: -Test) (E-g)mentioning

confidence: 99%

Heparin interacts with the adhesion GPCR GPR56, reduces receptor shedding, and promotes cell adhesion and motility

Chiang

Chang

Huang

et al. 2016

Journal of Cell Science

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“…Studies with the application of the HS blocking agent Surfen (Schuksz et al 2008) clearly showed reduced extracellular TG2 ), suggesting that if specific interference with TG2-syndecan 4 interactions could be achieved, then it would also serve as a therapeutic intervention site. Several HS binding sites within TG2 have been proposed (Lortat-Jacob et al 2012;Teesalu et al 2012). Our group have identified two distant basic amino acid clusters, RRWK (262-265) and KQKRK (598-602) which would come together to form a conformationally dependent high affinity binding site (Lortat-Jacob et al 2012).…”

Section: Tg2 As a Therapeutic Targetmentioning

confidence: 97%

“…HS chains have also high affinity binding for TG2 Lortat-Jacob et al 2012) which is associated with the HS chains of syndecan-4 in a variety of cell types Lortat-Jacob et al 2012;Nadella et al 2015;Wang et al 2011Teesalu et al 2012). HS proteoglycans have a physiopathological role in the kidney and have also been suggested to modulate TG2 trafficking in the kidney ).…”

Section: Heparan Sulfate Proteoglycans and Tg2 Export In Ckdmentioning

confidence: 99%

“…Several HS binding sites within TG2 have been proposed (Lortat-Jacob et al 2012;Teesalu et al 2012). Our group have identified two distant basic amino acid clusters, RRWK (262-265) and KQKRK (598-602) which would come together to form a conformationally dependent high affinity binding site (Lortat-Jacob et al 2012). Targeting this TG2 conformational heparin binding site, e.g.…”

Section: Tg2 As a Therapeutic Targetmentioning

confidence: 99%

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Transglutaminases: Expression in Kidney and Relation to Kidney Fibrosis

et al. 2015

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Enhanced Penetration and Retention of CuS‐Based Nanosystem Through NIR Light and In Situ Enzyme Response for Improved Tumor Therapy

Gao,

Zhu,

Jiang

et al. 2023

Adv Funct Materials

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The efficient way to increase the therapeutic efficacy of nanomedicines is by encouraging the penetration and enhancing the retention of nanoparticles at the tumor site. However, it is a serious dilemma that small nanoparticles can penetrate deep into the tumor tissue but easily be cleared into the surrounding tissues. In order to solve this dilemma, a smart nanosystem is created to address this problem, ensuring both the effective penetration of tiny nanoparticles (NPs) and their appropriate retention at the tumor site. CuS NPs that is modified with peptides are prepared facilely, and can aggregate in situ through the intermolecular crosslinking reaction catalyzed by the transglutaminase (TGase) abundantly expressed at the tumor site, resulting in an outstanding photothermal effect for tumor therapy. Upon NIR irradiation, the photothermal effect of CuS‐K and CuS‐Q induced the disintegration of liposomes and prompted the release of CuS‐K, CuS‐Q, and indocyanine green (ICG). Simultaneously, CuS‐K and CuS‐Q aggregated under the catalysis of TGase after being internalized by tumor cells to enhance photothermal therapy. The current study provides valuable inspiration to design nanomedicines with prolonged circulation time in the blood system, better penetration, and retention at the tumor site, and multimodal tumor therapy to achieve the desired therapeutic efficacy.

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Transglutaminase-2 Interaction with Heparin

Cited by 56 publications

References 51 publications

Heparin interacts with the adhesion GPCR GPR56, reduces receptor shedding, and promotes cell adhesion and motility

Heparin interacts with the adhesion GPCR GPR56, reduces receptor shedding, and promotes cell adhesion and motility

Transglutaminases: Expression in Kidney and Relation to Kidney Fibrosis

Enhanced Penetration and Retention of CuS‐Based Nanosystem Through NIR Light and In Situ Enzyme Response for Improved Tumor Therapy

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