Protein kinase C is activated in platelets subjected to pathological shear stress.

Kroll, Michael H.; Hellums, J. D.; Guo, Zhao-Zeng; Durante, William; Razdan, Kuldeep; Hrbolich, Janet K.; Schafer, Andrew I.

doi:10.1016/s0021-9258(18)53725-x

Cited by 95 publications

(18 citation statements)

References 44 publications

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“…Understanding the intracellular signaling mechanism induced by ligand binding to the platelet vWF receptor, GPIb-IX, as well as platelet signaling in general, has been hampered by the lack of specific means to interfere with platelet signaling intracellularly at a molecular level. Studies on the GPIb-IX-induced platelet activation by biochemical approaches have shown that ligand binding to GPIb-IX induces a series of intracellular biochemical changes such as generation of thromboxane A 2 (Kroll et al, 1991), production of phosphatidic acid (Kroll et al, 1991), activation of PI-3 kinase (Jackson et al, 1994), increase in the cytoplasmic calcium level (Kroll et al, 1991;Ikeda et al, 1993), and activation of protein kinases such as protein kinase C (Kroll et al, 1991(Kroll et al, , 1993Chow et al, 1992) and tyrosine kinases (Razdan et al, 1994;Asazuma et al, 1997). The consequence of these intracellular signaling events is the activation of integrin ␣ IIb ␤ 3 (De Marco et al, 1985a,b;Gralnick et al, 1985;Kroll et al, 1991;Savage et al, 1992Savage et al, , 1996.…”

Section: Discussionmentioning

confidence: 99%

“…2). These inhibitors also inhibit vWFinduced integrin activation in platelets (Coller, 1981;De Marco et al, 1985a;Savage et al, 1992;Kroll et al, 1993;Kroll et al, 1991Kroll et al, , 1993. Reconstitution of the platelet GPIb-IX-mediated activation of ␣ IIb ␤ 3 in CHO cells is thus significant to further understanding the GPIb-IXmediated signaling using specific molecular biological approaches.…”

Section: Discussionmentioning

confidence: 99%

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Analysis of the Roles of 14-3-3 in the Platelet Glycoprotein Ib-IX–Mediated Activation of Integrin αIIbβ3 Using a Reconstituted Mammalian Cell Expression Model

Englund

et al. 1999

The Journal of Cell Biology

126

137

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We have reconstituted the platelet glycoprotein (GP) Ib-IX–mediated activation of the integrin αIIbβ3 in a recombinant DNA expression model, and show that 14-3-3 is important in GPIb-IX signaling. CHO cells expressing αIIbβ3 adhere poorly to vWF. Cells expressing GPIb-IX adhere to vWF in the presence of botrocetin but spread poorly. Cells coexpressing integrin αIIbβ3 and GPIb-IX adhere and spread on vWF, which is inhibited by RGDS peptides and antibodies against αIIbβ3. vWF binding to GPIb-IX also activates soluble fibrinogen binding to αIIbβ3 indicating that GPIb-IX mediates a cellular signal leading to αIIbβ3 activation. Deletion of the 14-3-3–binding site in GPIbα inhibited GPIb-IX–mediated fibrinogen binding to αIIbβ3 and cell spreading on vWF. Thus, 14-3-3 binding to GPIb-IX is important in GPIb-IX signaling. Expression of a dominant negative 14-3-3 mutant inhibited cell spreading on vWF, suggesting an important role for 14-3-3. Deleting both the 14-3-3 and filamin-binding sites of GPIbα induced an endogenous integrin-dependent cell spreading on vWF without requiring αIIbβ3, but inhibited vWF-induced fibrinogen binding to αIIbβ3. Thus, while different activation mechanisms may be responsible for vWF interaction with different integrins, GPIb-IX–mediated activation of αIIbβ3 requires 14-3-3 interaction with GPIbα.

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Section: Discussionmentioning

confidence: 99%

Section: Discussionmentioning

confidence: 99%

Analysis of the Roles of 14-3-3 in the Platelet Glycoprotein Ib-IX–Mediated Activation of Integrin αIIbβ3 Using a Reconstituted Mammalian Cell Expression Model

Englund

et al. 1999

The Journal of Cell Biology

126

137

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“…Binding of multimeric von Willebrand Factor (vWF) to its adhesive receptor on the platelet surface, the glycoprotein (GP) Ib-IX-V complex, whether induced by shear stress, or by the vWF modulators, ristocetin or botrocetin, transmits an intracellular signal and activates platelets, as measured by elevation of intracellular Ca 2+ and phosphorylation of cytoplasmic proteins (De Marco & Shapiro, 1981;Kroll et al, 1991Kroll et al, , 1993Ikeda et al, 1993;Clemetson, 1995;Ozaki et al, 1995). In shear-induced platelet aggregation, platelet activation enables a secondary phase of GP IIb-IIIa complexmediated aggregation that stabilizes the platelet aggregate.…”

Section: Discussionmentioning

confidence: 99%

Binding of Purified 14-3-3 ζ Signaling Protein to Discrete Amino Acid Sequences within the Cytoplasmic Domain of the Platelet Membrane Glycoprotein Ib-IX-V Complex

et al. 1998

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The glycoprotein (GP) Ib-IX-V complex constitutively expressed on the platelet plasma membrane mediates initial adhesion of circulating platelets to vessel wall matrix at high shear, and shear-induced platelet aggregation. In both cases, this involves binding of GP Ib-IX-V to the adhesive glycoprotein, von Willebrand Factor (vWF). vWF binding to GP Ib-IX-V rapidly induces platelet activation, leading to cytoskeletal rearrangement, shape change, and secretion that enables alphaIIbbeta3 integrin (GP IIb-IIIa)-dependent platelet aggregation. All these events are critical in (patho)physiological thrombus formation. The recent discovery that the signaling protein, 14-3-3 zeta, copurifies with the GP Ib-IX complex (minus GP V) [Du, X., Harris, S. J., Tetaz, T. J., Ginsberg, M. H., & Berndt, M. C. (1994) J. Biol. Chem. 269, 18287-18290] indicated a potential mechanism for vWF-dependent signaling. The aim of the present study was to identify discrete amino acid sequences that bind 14-3-3 zeta within the cytoplasmic domain of the receptor. As an initial screening assay, overlapping synthetic peptides based on the cytoplasmic domains of GP Ibalpha (100 residues), GP Ibbeta (34 residues), GP IX (5 residues), and GP V (16 residues) were immobilized and assessed for the ability to bind purified 14-3-3 zeta. The C-terminal sequence GHSL of GP Ibalpha was identified as one 14-3-3 zeta interactive sequence, consistent with previous results [Du, X., Fox, J. E., & Pei, S. (1996) J. Biol. Chem. 271, 7362-7367]. Binding of 125I-labeled 14-3-3 zeta to GHSL-containing peptides was inhibitable by unlabeled 14-3-3 zeta and by anti-14-3-3 zeta IgG. Ala-walking through the GHSL sequence suggested all residues were necessary for optimal binding. In addition, 14-3-3 zeta bound with lower affinity to a peptide based on the central region of the GP Ibalpha cytoplasmic domain (Arg-557-Gly-575), whereas peptide sequences within the cytoplasmic domains of GP Ibbeta (Arg-160-Arg-175) and GP V (Lys-529-Gly-544) bound 14-3-3 zeta with comparable affinity to the GHSL-containing peptide. Soluble GHSL-containing peptides, GP Ibbeta- and GP V-based peptides semidissociated 14-3-3 zeta from GP Ib-IX-V or GP Ib-IX in platelet extracts as analyzed by immunoprecipitation, suggesting these sequences, at least partially, mediate the GP Ib-IX-V-14-3-3 zeta interaction in cells. Further, phosphorylation of the GP Ibbeta peptide at a site corresponding to a protein kinase A phosphorylation site (Ser-166) enhanced the affinity of 14-3-3 zeta binding by approximately 8-fold, suggesting phosphorylation as a potential mechanism for regulating 14-3-3 zeta association with the GP Ib-IX-V complex.

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“…Due to intimal fibrous hyperplasia, vascular grafts sometimes become stenotic (narrow) either at the anastomotic regions or along the inner wall of the grafts [1][2][3], leading to elevated shear forces on flowing platelets. Such higher shear forces have been shown to increase platelet concentration near the wall [4], and to induce intracellular signaling cascades characterized by binding of von Willebrand factor (vWF) to glycoprotein GPIbα [5], Ca 2+ mobilization [6,7], actin polymerization and cytoskeletal rearrangements [8], protein kinase C expression [9], and GPIIb/IIIa activation [10]. Mechanical damage of platelets due to elevated shear forces may cause lysis [11], resulting in the release of procoagulant factors.…”

Section: Introductionmentioning

confidence: 99%

Downstream platelet adhesion and activation under highly elevated upstream shear forces

Rahman

Hlady

2019

Acta Biomaterialia

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Elevated shear force caused by an anastomotic stenosis is a common complication at the blood vessel-vascular implant interface. Although elevated shear forces were found to cause platelet aggregation around a stenotic region, transient platelet exposure to elevated shear forces and subsequent downstream events occurring under lower shear force were not extensively studied. We hypothesize that effects of elevated shear forces on pre-activation of platelets for downstream adhesion and activation are relevant in understanding the increased thrombotic risk associated with blood-contacting devices. We designed a microfluidic flow system to mimic the hemodynamic environment of vasculature with an upstream anastomotic stenosis with five wall shear strain rates ranging from 1620 s −1 to 11560 s −1 . Under shear flow conditions, transient exposure of whole blood to elevated shear forces resulted in higher downstream platelet adhesion onto three different immobilized platelet agonists: fibrinogen, collagen, or von Willebrand factor. Platelet expression of four activation markers (P-selectin, GPIIb/IIIa, lysosomal glycoprotein, and phosphatidylserine) significantly increased after transient exposure to higher upstream wall shear strain rates of 2975 -11560 s −1 . A significant lysis was observed when platelets were primed by upstream wall shear strain rate of 11560 s −1 . These experimental results could be helpful to understand how altered hemodynamics around an anastomotic stenosis promotes thrombus formation downstream.

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Protein kinase C is activated in platelets subjected to pathological shear stress.

Cited by 95 publications

References 44 publications

Analysis of the Roles of 14-3-3 in the Platelet Glycoprotein Ib-IX–Mediated Activation of Integrin αIIbβ3 Using a Reconstituted Mammalian Cell Expression Model

Analysis of the Roles of 14-3-3 in the Platelet Glycoprotein Ib-IX–Mediated Activation of Integrin αIIbβ3 Using a Reconstituted Mammalian Cell Expression Model

Binding of Purified 14-3-3 ζ Signaling Protein to Discrete Amino Acid Sequences within the Cytoplasmic Domain of the Platelet Membrane Glycoprotein Ib-IX-V Complex

Downstream platelet adhesion and activation under highly elevated upstream shear forces

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