C-terminal peptide of thrombospondin-1 induces platelet aggregation through the Fc receptor γ-chain–associated signaling pathway and by agglutination

Tulasne, David; Judd, Barbi A.; Johansen, Mette L.; Asazuma, Naoki; Best, Denise; Brown, Eric J.; Kahn, Mark L.; Koretzky, Gary A.; Watson, Steve P.

doi:10.1182/blood.v98.12.3346

Cited by 48 publications

(75 citation statements)

References 41 publications

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“…We further show that CD47 ligation differentially activates and inactivates ␣ v ␤ 3 and ␣ 4 ␤ 1 in melanoma cells and ␣ 4 ␤ 1 and ␣ 5 ␤ 1 in Jurkat cells. Unexpectedly, but consistent with a recent report demonstrating CD47-independent induction of platelet aggregation by a CD47-binding peptide from TSP1 (22), we found that effects of the CD47-binding peptide derived from TSP1 on ␣ 4 ␤ 1 -dependent T cell adhesion are CD47-independent.…”

supporting

confidence: 78%

“…Activity of these TSP1 peptides in CD47-deficient platelets was partially dependent on FcR ␥ expression (22), but Jurkat cells do not express this receptor (47) and do not show the same sensitivity to Src inhibition as was reported in platelets (22). Understanding the role of CD47 in response to the TSP1 peptide is further complicated by our observation that the CD47-independent pathway shares the sensitivity to pertussis toxin that characterizes CD47 signaling.…”

Section: A Cd47-binding Peptide Stimulatesmentioning

confidence: 55%

“…CD47-mediated responses to the TSP1 peptides were shown previously to require pertussis toxin-sensitive G proteins (6,9,14,17), whereas the CD47-independent activity of these peptides reported in platelets was sensitive to Src inhibitors (22). Remarkably, the stimulation by FIRVVMYEGKK of adhesion on limiting concentrations of TSP1 or NoC2 was equally sensitive to pertussis toxin in both the wild type and CD47-deficient Jurkat cells (Fig.…”

Section: A Cd47-binding Peptide Stimulatesmentioning

confidence: 76%

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Regulation of Integrin Function by CD47 Ligands

Barazi

Cashel

et al. 2002

Journal of Biological Chemistry

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CD47 (integrin-associated protein) is an integral membrane protein that is required for granulocyte and T cell recruitment to sites of infection (1, 2), and its absence on red blood cells leads to their rapid macrophage-mediated clearance (3). CD47 may also function as a costimulator to regulate T cell activation, survival, and Th1 versus Th2 differentiation (4, 5). Endogenous ligands for the extracellular domain of CD47 include the secreted protein thrombospondin-1 (TSP1) 1 and potentially other members of the thrombospondin family, several integrins (6 -9), and some members of the signal-regulatory protein family (3, 10 -13). Engagement of CD47 by soluble ligands or signal-regulatory protein counter receptors modulates several cell signaling pathways, including activation of a heterotrimeric G protein (14).Although some signal transduction through CD47 is integrin-independent (4, 15, 16), association of CD47 with certain integrins was found to modulate their function to mediate cell adhesion or motility (6,8,9,17). In addition to its known functional and physical interactions with ␣ v ␤ 3 , ␣ IIb ␤ 3 , and ␣ 2 ␤ 1 integrins, several publications have suggested an association of CD47 with ␣ 4 ␤ 1 integrin. CD47 and ␣ 4 ␤ 1 were colocalized on microvilli of K562 erythroleukemia cells (18), and CD47-dependent arrest of T cells on inflammatory endothelium could be blocked by antibodies that prevent ␣ 4 ␤ 1 integrin binding to VCAM-1 (2). In the latter study, ligation of CD47 by TSP1 or signal-regulatory protein 1␣ was inferred to activate ␣ 4 ␤ 1 integrin on T cells, although this was not demonstrated either functionally or biochemically.We recently found that CD47 expression is required for stimulation of T cell motility and expression of MMP-2 stimulated by ␣ 4 ␤ 1 integrin ligands (19). An antibody to CD47 also blocked the motility response to an ␣ 4 ␤ 1 integrin ligand (19). Therefore, at least a functional interaction occurs between CD47 and ␣ 4 ␤ 1 integrin.We identified a binding site for ␣ 4 ␤ 1 integrin in the Nterminal domains of TSP1 and TSP2 (19), whereas two binding sites for CD47 have been localized to the C-terminal domain of TSP1 (for review, see Ref. 20). Thus, TSP1 could potentially regulate its own interaction with ␣ 4 ␤ 1 integrin through simultaneous interactions with CD47 and ␣ 4 ␤ 1 integrin on a T cell, analogous to the ability of soluble TSP1 to stimulate ␣ v ␤ 3 integrin-dependent melanoma cell adhesion to immobilized TSP1 (21).To define a molecular basis for functional cross-talk between these two receptors, we have examined the effect of CD47 ligands on the function of ␣ 4 ␤ 1 integrin in T cells and melanoma cells. We confirmed that ligation of CD47 can activate ␣ 4 ␤ 1 integrin function but unexpectedly found the mechanism of this activity to be CD47 ligand-dependent. We further show that CD47 ligation differentially activates and inactivates ␣ v ␤ 3 and ␣ 4 ␤ 1 in melanoma cells and ␣ 4 ␤ 1 and ␣ 5 ␤ 1 in Jurkat cells. Unexpectedly, but consistent with a recent report demonstrating C...

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supporting

confidence: 78%

Section: A Cd47-binding Peptide Stimulatesmentioning

confidence: 55%

Section: A Cd47-binding Peptide Stimulatesmentioning

confidence: 76%

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Regulation of Integrin Function by CD47 Ligands

Barazi

Cashel

et al. 2002

Journal of Biological Chemistry

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“…We therefore tested the ability of 4N1K to enhance ␣ v ␤ 3 avidity by measuring OV-10 cell binding to AP3-coated plates, at coating concentrations that supported only nonspecific attachment by untreated cells. Although 4N1K has been reported to have CD47-independent effects on integrin functions in some situations (25,26), no increased binding with peptide treatment was observed for CD47-deficient cells (Fig. 3B).…”

Section: N1k Treatment Promotes Igv-␣ V ␤ 3 Interactionsmentioning

confidence: 86%

Cholesterol-independent Interactions with CD47 Enhance αvβ3 Avidity

McDonald

Zheleznyak

Frazier

2004

Journal of Biological Chemistry

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Expression in OV10 cells of either wild-type CD47 or its extracellular IgV domain linked to a glycosylphosphatidylinositol anchor-(IgV-GPI) enhanced ligand-induced ␣ v ␤ 3 activation as detected by the binding of LIBS1 and LIBS6 mAbs. The amplitude of LIBS binding was greater with both CD47 and IgV-GPI expression, indicating an increase in the population of "activable" integrin molecules. Expression of either CD47 species also increased ␣ v ␤ 3 -mediated adhesion to vitronectin, and to surfaces coated with the anti-␤ 3 antibody AP3, because of enhanced clustering of ␣ v ␤ 3 as confirmed by chemical cross-linking. Cholesterol depletion with methyl-␤-cyclodextrin did not prevent the increase in anti-LIBS binding, but reduced cell adhesion to vitronectin and AP3. However, cells expressing CD47 were partially insulated against this disruption, and IgV-GPI was even more effective. Both CD47 and IgV-GPI were found in cholesterol-rich rafts prepared in the absence of detergent, but only CD47 could recruit ␣ v ␤ 3 and its associated signaling molecules to these domains. Thus CD47-␣ v ␤ 3 complexes in cholesterol-rich raft domains appear to engage in G i -dependent signaling whereas CD47-␣ v ␤ 3 interactions that lead to integrin clustering are also detergent resistant, but are insensitive to cholesterol depletion and do not require the transmembrane region of CD47.

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“…A potential conformation change that exposes one of the VVM sequences has been proposed based on dynamic modeling studies (54), but structure function and mutagenesis studies have not been performed to determine whether the VVM sequences are involved in binding of native TSP1 to CD47. Furthermore, both TSP1-derived CD47 binding peptides have well-documented CD47-independent activities, and they cannot be used as reliable surrogates for TSP1 to investigate CD47 signaling (9,129,279).…”

Section: Fig 2 Overview Of Matricellular Protein Functions In Cellumentioning

confidence: 99%

Regulation of Cellular Redox Signaling by Matricellular Proteins in Vascular Biology, Immunology, and Cancer

Roberts

Kaur

Isenberg

2017

Antioxidants & Redox Signaling

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Significance: In contrast to structural elements of the extracellular matrix, matricellular proteins appear transiently during development and injury responses, but their sustained expression can contribute to chronic disease. Through interactions with other matrix components and specific cell surface receptors, matricellular proteins regulate multiple signaling pathways, including those mediated by reactive oxygen and nitrogen species and H 2 S. Dysregulation of matricellular proteins contributes to the pathogenesis of vascular diseases and cancer. Defining the molecular mechanisms and receptors involved is revealing new therapeutic opportunities. Recent Advances: Thrombospondin-1 (TSP1) regulates NO, H 2 S, and superoxide production and signaling in several cell types. The TSP1 receptor CD47 plays a central role in inhibition of NO signaling, but other TSP1 receptors also modulate redox signaling. The matricellular protein CCN1 engages some of the same receptors to regulate redox signaling, and ADAMTS1 regulates NO signaling in Marfan syndrome. In addition to mediating matricellular protein signaling, redox signaling is emerging as an important pathway that controls the expression of several matricellular proteins. Critical Issues: Redox signaling remains unexplored for many matricellular proteins. Their interactions with multiple cellular receptors remains an obstacle to defining signaling mechanisms, but improved transgenic models could overcome this barrier. Future Directions: Therapeutics targeting the TSP1 receptor CD47 may have beneficial effects for treating cardiovascular disease and cancer and have recently entered clinical trials. Biomarkers are needed to assess their effects on redox signaling in patients and to evaluate how these contribute to their therapeutic efficacy and potential side effects. Antioxid. Redox Signal. 27, 874-911.

show abstract

C-terminal peptide of thrombospondin-1 induces platelet aggregation through the Fc receptor γ-chain–associated signaling pathway and by agglutination

Cited by 48 publications

References 41 publications

Regulation of Integrin Function by CD47 Ligands

Regulation of Integrin Function by CD47 Ligands

Cholesterol-independent Interactions with CD47 Enhance αvβ3 Avidity

Regulation of Cellular Redox Signaling by Matricellular Proteins in Vascular Biology, Immunology, and Cancer

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