Glycoprotein VI is the collagen receptor in platelets which underlies tyrosine phosphorylation of the Fc receptor ??-chain

Gibbins, Jonathan M.; Okuma, Minoru; Farndale, Richard W.; Barnes, Michael J.; Watson, SP

doi:10.1097/00001721-199710000-00016

Cited by 105 publications

(155 citation statements)

References 8 publications

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“…However, though FcR␥ was traditionally viewed as a signaling chain exclusively linked to FcR function, a number of non-FcR cell surface molecules have recently been shown to signal through FcR␥. These include GpVI, the collagen receptor of platelets (35,36); the paired Ig-like receptor PIR-A on multiple lineages of the immune system (37-39); the osteoclast-specific OSCAR protein (40,41); and the recently described DCAR molecule on dendritic cells (42). In agreement with the role of FcR␥ in non-FcR functions, FcR␥ Ϫ/Ϫ neutrophils also failed to respond to certain stimuli that are clearly not expected to signal through FcRs (A. M. and C. A. L., unpublished observation).…”

Section: Discussionmentioning

confidence: 99%

Responses of Neutrophils to Anti-Integrin Antibodies Depends on Costimulation through Low Affinity FcγRs: Full Activation Requires Both Integrin and Nonintegrin Signals

Jakus

Berton

Ligeti

et al. 2004

The Journal of Immunology

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The relative contribution of integrin and nonintegrin signals to neutrophil activation is incompletely understood. Immobilized anti-integrin Abs were previously shown to induce robust activation of neutrophils without any additional stimulus, suggesting that cross-linking of integrins is sufficient for full activation of the cells. However, the possible contribution from other receptors has not been tested in this system. In this study, we show that neutrophil responses to anti-integrin Abs requires costimulation through low-affinity FcγRs. Murine neutrophils lacking the FcR γ-chain or FcγRIII failed to respond to immobilized Abs against β1, β2, or β3 integrins and the activation of wild-type cells could be prevented by blocking Abs against FcγRII/III. Plate-bound anti-CD18 Abs initiated a respiratory burst from human neutrophils, but this response was abrogated when the F(ab′)2 of the same Abs were used or the cells were preincubated with FcγRIIA-blocking Abs. Lack of FcγRIII or administration of FcγR-blocking Abs had no effect on responses of TNF-stimulated cells plated on fibrinogen or rICAM-1. TNF restored the respiratory burst of FcγRIII-deficient neutrophils plated on anti-CD18 mAbs. The p38 MAPK inhibitor SB203580 attenuated the responses of neutrophils to anti-CD18 mAbs or TNF stimulation on a fibrinogen surface. Taken together, these results indicate that activation of low-affinity FcγRs is required for neutrophil responses induced by anti-integrin Abs and suggest that a second coactivation signal (e.g., through TNF or FcR ligation) is indispensable for full integrin-mediated activation of neutrophils. These second signals are interchangeable and they may converge on the p38 MAPK.

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Section: Discussionmentioning

confidence: 99%

Responses of Neutrophils to Anti-Integrin Antibodies Depends on Costimulation through Low Affinity FcγRs: Full Activation Requires Both Integrin and Nonintegrin Signals

Jakus

Berton

Ligeti

et al. 2004

The Journal of Immunology

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“…GPVI is associated with the Fc receptor g-chain (FcR g-chain) on the platelet surface [4,5], and crosslinking leads to phosphorylation of the FcR g-chain on a sequence known as an immunoreceptor tyrosine-based activation motif (ITAM) [6], probably by a Src kinase [7,8]. This enables binding and activation of the tyrosine kinase Syk, starting a chain of events that leads to tyrosine phosphorylation of phospholipase C g2 (PLCg2).…”

Section: There Is Evidence For Minor Roles Of Other Receptors In Thesmentioning

confidence: 99%

“…6A (for 12G10, TS2/16 and N29). In contrast, a large number of studies have described tyrosine phosphorylation in platelets following crosslinking of other surface receptors using specific antibodies including GPVI [4,37] and FcgRIIA [38].…”

mentioning

confidence: 99%

Evidence against a direct role of the integrin α2β1 in collagen‐induced tyrosine phosphorylation in human platelets

Hers

Berlanga

Tiekstra

et al. 2000

European Journal of Biochemistry

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In the present study we have investigated whether the collagen receptor a2b1 (GPIa-IIa; GP, glycoprotein) regulates protein tyrosine phosphorylation in platelets directly through activation of tyrosine kinases or indirectly through modification of the response to GPVI. The interaction of collagen with a2b1 was inhibited in two distinct ways, using the metalloprotease jararhagin, which cleaves the b1 subunit, or the antibody P1E6 which competes with binding of collagen to the integrin. The two inhibitors caused a shift to the right in the collagen concentration response curves for protein tyrosine phosphorylation and platelet activation consistent with a causal relationship between the two events. There was no change in the overall pattern of tyrosine phosphorylation in response to high concentrations of collagen in the presence of a2b1 blockade demonstrating that the integrin is not required for this event. In contrast, jararhagin and P1E6 had a small, almost negligible inhibitory effect against responses to the GPVI-selective agonist collagen-related peptide (CRP) and the G protein-coupled receptor agonist thrombin. Crosslinking of a2b1 in solution or by adhesion to a monolayer using a variety of antibodies to either subunit of the integrin did not induce detectable protein tyrosine phosphorylation in whole cell lysates. The snake venom toxin trimucytin-stimulated a similar pattern of tyrosine phosphorylation to that induced by crosslinking of GPVI which was maintained in the presence of jararhagin. Trimucytin may therefore induce activation via GPVI rather than a2b1 as previously thought. These observations show that the integrin a2b1 is not required for regulation of tyrosine phosphorylation by collagen.Keywords: collagen; GPIa-IIa; GPVI; platelets; tyrosine phosphorylation.When the subendothelium lining is damaged, platelets adhere to newly exposed collagen fibres and undergo activation leading to thromboxane A 2 formation, aminophospholipid exposure, granule secretion and platelet aggregation. Several surface glycoproteins have been implicated as collagen receptors, including glycoprotein (GP) IV (also known as CD36), GPVI, a recently cloned protein of 65 kDa protein, a 85/90 kDa protein and the integrin a2b1. GPVI and a2b1 are believed to play pivotal roles in the interaction of platelets with collagen as patients deficient in the expression of either protein have impaired collagen±platelet interactions and mild bleeding disorders. The consensus is that the integrin a2b1 plays a critical role in adhesion, whilst GPVI is essential for activation. There is evidence for minor roles of other receptors in these responses (reviewed in [1±3]).GPVI is associated with the Fc receptor g-chain (FcR g-chain) on the platelet surface [4,5], and crosslinking leads to phosphorylation of the FcR g-chain on a sequence known as an immunoreceptor tyrosine-based activation motif (ITAM) [6], probably by a Src kinase [7,8]. This enables binding and activation of the tyrosine kinase Syk, starting a chain of events that leads to t...

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“…Contact of circulating platelets with exposed collagen leads to platelet activation, resulting in platelet aggregation. Adhesion of platelets to collagen is mediated mainly by integrin ␣2␤1, whereas activation is mediated by the signal-transducing glycoprotein VI (GPVI) 3 (1,2). GPVI is a platelet collagen receptor that is constitutively associated with the Fc receptor ␥-chain (FcR␥) (3,4).…”

mentioning

confidence: 99%

“…Adhesion of platelets to collagen is mediated mainly by integrin ␣2␤1, whereas activation is mediated by the signal-transducing glycoprotein VI (GPVI) 3 (1,2). GPVI is a platelet collagen receptor that is constitutively associated with the Fc receptor ␥-chain (FcR␥) (3,4). FcR␥ is phosphorylated by SFK (Src family kinase) at the tyrosine residue in its immunoreceptor tyrosine-based activation motif (ITAM) upon GPVI-collagen binding, and the tyrosine kinase Syk (spleen tyrosine kinase) binds to the ITAM and becomes autophosphorylated (5)(6)(7)(8).…”

mentioning

confidence: 99%

RhoG Protein Regulates Glycoprotein VI-Fc Receptor γ-Chain Complex-mediated Platelet Activation and Thrombus Formation

Kim

Dangelmaier

Bhavanasi

et al. 2013

Journal of Biological Chemistry

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Background: RhoG is a ubiquitously expressed member of the Rho family of GTPases. Results: RhoG-deficient platelets display severely impaired GPVI-dependent platelet activation. Conclusion: RhoG plays an important role in GPVI-FcR␥ complex-mediated platelet activation and thrombus formation. Significance: Our study enhances the understanding of the molecular mechanisms of GPVI-FcR␥ complex activation.

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Glycoprotein VI is the collagen receptor in platelets which underlies tyrosine phosphorylation of the Fc receptor ??-chain

Cited by 105 publications

References 8 publications

Responses of Neutrophils to Anti-Integrin Antibodies Depends on Costimulation through Low Affinity FcγRs: Full Activation Requires Both Integrin and Nonintegrin Signals

Responses of Neutrophils to Anti-Integrin Antibodies Depends on Costimulation through Low Affinity FcγRs: Full Activation Requires Both Integrin and Nonintegrin Signals

Evidence against a direct role of the integrin α2β1 in collagen‐induced tyrosine phosphorylation in human platelets

RhoG Protein Regulates Glycoprotein VI-Fc Receptor γ-Chain Complex-mediated Platelet Activation and Thrombus Formation

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