Protein-Protein Interactions in Platelet α<sub>IIb</sub>β<sub>3</sub>Signaling

Buensuceso, Charito; Arias-Salgado, Elena G; Shattil, Sanford J.

doi:10.1055/s-2004-833478

Cited by 17 publications

(15 citation statements)

References 114 publications

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“…In agreement with the aggregation data, there was no significant difference in PE-conjugated JonA staining ( Figure 6C), which suggests that depletion of STXBP5 did not affect integrin αIIbβ3 activation (15,44,45). Electron microscopy (EM) analysis detected no overt morphology differences in Stxbp5 KO platelets (Supplemental Figure 2).…”

Section: Stxbp5 Is Important For Platelet Secretionsupporting

confidence: 75%

Platelet secretion and hemostasis require syntaxin-binding protein STXBP5

Ye¹,

Huang²,

Joshi³

et al. 2014

J. Clin. Invest.

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Section: Stxbp5 Is Important For Platelet Secretionsupporting

confidence: 75%

Platelet secretion and hemostasis require syntaxin-binding protein STXBP5

Ye¹,

Huang²,

Joshi³

et al. 2014

J. Clin. Invest.

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“…The integrin cytoplasmic tails, including those of the αIIb and β3 subunits, are generally short and do not have any known catalytic activity. Searches to define other mechanisms of integrin signaling have led to the identification of multiple cytoskeletal and signaling proteins that directly associate with the cytoplasmic tails of either the α-or β-subunits and influence the integrin-induced signaling (reviewed in Buensuceso et al, 2004;Liu et al, 2000;Phillips et al, 2001). A recent focus of such studies has been the association and functional consequences the nonreceptor tyrosine kinases, including specific SFKs in regulating integrin signaling (Arias-Salgado et al, 2003;Arias-Salgado et al, 2005;Obergfell et al, 2002).…”

Section: Discussionmentioning

confidence: 99%

“…Since they do not exhibit any intrinsic enzymatic activity, changes in the proteins associated with these cytoplasmic tails are presumed to be involved in the propagation of outside-in signaling. Many such integrin-associated proteins have been identified, and include cytoskeletal, adaptor and known signaling proteins (reviewed in Buensuceso et al, 2004;Liu et al, 2000;Ma et al, 2007;Phillips et al, 2001). Some of these associated proteins appear to regulate inside-out signaling (Bertoni et al, 2002;Calderwood et al, 1999;Ma et al, 2007;Vinogradova et al, 2002), and a variety of signaling molecules, such as calpain, Rho-family GTPases, tyrosine kinases and lipid kinases, are activated as a consequence of outside-in signaling (Barry et al, 1997;Ferrell, Jr and Martin, 1989;Fox and Phillips, 1983;Fox et al, 1993;Frangioni et al, 1993;Golden et al, 1990;King et al, 1997;Laudanna et al, 1996;Lipfert et al, 1992;Price et al, 1998;Renshaw et al, 1996).…”

Section: Introductionmentioning

confidence: 99%

Analysis of Fyn function in hemostasis and αIIbβ3-integrin signaling

Reddy

Smith

Plow

2008

Journal of Cell Science

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Recent studies have shown that Src-family kinases (SFKs) play an important role in mediating integrin signalling, and the β3 subunit of αIIbβ3 integrin has been shown to interact with multiple SFK members. Here, we analyzed the interactions and functional consequences of Fyn and Src binding to αIIbβ3. Fyn associated with the β3 subunit in resting and thrombin-aggregated platelets, whereas interaction between Src and αIIbβ3 was seen predominantly in resting but not in thrombin-aggregated platelets. We have also observed that Fyn but not Src localized to focal adhesions in CHO cells adherent to fibrinogen through αIIbβ3. On the basis of these differences, we wanted to determine the sequence requirements for the interaction of Fyn and Src within the β3-cytoplasmic domain. Whereas Src association required the C-terminal region of β3, Fyn continued to interact with mutants that could no longer associate with Src and that contained as few as 13 membrane-proximal amino acids of the β3-cytoplasmic tail. Using deletion mutants of β3-cytoplasmic tails expressed as GST-fusion proteins, we narrowed down the Fyn-binding site even further to the amino acid residues 721-725 (IHDRK) of the β3-cytoplasmic domain. On the basis of these observations, we explored whether Fyn–/– mice exhibited any abnormalities in hemostasis and platelet function. We found that Fyn–/– mice significantly differed in their second bleeding times compared with wild-type mice, and platelets from Fyn–/– mice exhibited delayed spreading on fibrinogen-coated surfaces. Using mutant forms of Fyn, it appears that its kinase activity is required for its localization to focal adhesions and to mediate αIIbβ3-dependent cell spreading. Our results suggest that Fyn and Src have distinct requirements for interaction with αIIbβ3; and, consequently, the two SFK can mediate different functional responses.

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“…Activated integrin ␣ IIb ␤ 3 also contributes to the platelet activation process (41). This so-called outside-in signaling by the integrin relies on the clustering of ligand-occupied integrins.…”

Section: B Platelet Integrins and Other Adhesive Receptorsmentioning

confidence: 99%

New Fundamentals in Hemostasis

Versteeg

Heemskerk

Levi

et al. 2013

Physiological Reviews

912

831

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Hemostasis encompasses the tightly regulated processes of blood clotting, platelet activation, and vascular repair. After wounding, the hemostatic system engages a plethora of vascular and extravascular receptors that act in concert with blood components to seal off the damage inflicted to the vasculature and the surrounding tissue. The first important component that contributes to hemostasis is the coagulation system, while the second important component starts with platelet activation, which not only contributes to the hemostatic plug, but also accelerates the coagulation system. Eventually, coagulation and platelet activation are switched off by blood-borne inhibitors and proteolytic feedback loops. This review summarizes new concepts of activation of proteases that regulate coagulation and anticoagulation, to give rise to transient thrombin generation and fibrin clot formation. It further speculates on the (patho)physiological roles of intra-and extravascular receptors that operate in response to these proteases. Furthermore, this review provides a new framework for understanding how signaling and adhesive interactions between endothelial cells, leukocytes, and platelets can regulate thrombus formation and modulate the coagulation process. Now that the key molecular players of coagulation and platelet activation have become clear, and their complex interactions with the vessel wall have been mapped out, we can also better speculate on the causes of thrombosis-related angiopathies.

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Protein-Protein Interactions in Platelet α_IIbβ₃Signaling

Abstract: El artículo seleccionado no se encuentra disponible por ahora a texto completo por no haber sido facilitado todavía por el investigador a cargo del archivo del mismo.

Cited by 17 publications

References 114 publications

Platelet secretion and hemostasis require syntaxin-binding protein STXBP5

Platelet secretion and hemostasis require syntaxin-binding protein STXBP5

Analysis of Fyn function in hemostasis and αIIbβ3-integrin signaling

New Fundamentals in Hemostasis

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Protein-Protein Interactions in Platelet αIIbβ3Signaling

Abstract: El artículo seleccionado no se encuentra disponible por ahora a texto completo por no haber sido facilitado todavía por el investigador a cargo del archivo del mismo.

Cited by 17 publications

References 114 publications

Platelet secretion and hemostasis require syntaxin-binding protein STXBP5

Platelet secretion and hemostasis require syntaxin-binding protein STXBP5

Analysis of Fyn function in hemostasis and αIIbβ3-integrin signaling

New Fundamentals in Hemostasis

Contact Info

Product

Resources

About

Protein-Protein Interactions in Platelet α_IIbβ₃Signaling