ERK2 activation in arteriolar and venular murine thrombosis: platelet receptor GPIb vs. P2X.

in Journal of Thrombosis and Haemostasis [=JTH] (2006)

The functional significance of extracellular signal-regulated kinase 2 (ERK2) activation was investigated during shear induced human platelet aggregation (SIPA) in vitro and during shear controlled ... [more ▼]

The functional significance of extracellular signal-regulated kinase 2 (ERK2) activation was investigated during shear induced human platelet aggregation (SIPA) in vitro and during shear controlled thrombosis in vivo in intestinal arterioles and venules of wild type (WT) and transgenic (TG) mice with platelet-specific overexpression of human P2X(1) (TG). The conclusions are that P2X(1) and ERK2 both participate in shear stress controlled thrombosis, but ERK2 activation is initiated predominantly via GPIb-VWF interactions. [less ▲]

P2X1-mediated ERK2 activation amplifies the collagen-induced platelet secretion by enhancing myosin light chain kinase activation.

in Journal of Biological Chemistry (2003)

This study shows that, at low doses of collagen, glycoprotein VI activation leads to early protein kinase C- and MLC kinase-dependent platelet degranulation. Rapidly released ATP triggers P2X1 -mediated ... [more ▼]

This study shows that, at low doses of collagen, glycoprotein VI activation leads to early protein kinase C- and MLC kinase-dependent platelet degranulation. Rapidly released ATP triggers P2X1 -mediated Ca2+ influx, activating ERK2, in turn amplifying platelet secretion by reinforcing the early MLC kinase phosphorylation. Hence, the P2X1-ERK2-MLC axis contributes to collagen-induced platelet activation by enhancing platelet degranulation. [less ▲]

Overexpression of the platelet P2X1 ion channel.in transgenic mice generates a novel prothrombotic phenotype.

in Journal of Thrombosis and Haemostasis [=JTH] (2003)

The intracellular tyrosine residues of the ATP-gated P2X(1) ion channel are essential for its function.

in FEBS Letters (2002)

In this study, we mutated the four highly conserved intracellular tyrosine residues of the P2X(1) ion channel were mutated into phenylalanine. Simultaneous electrophysiological and calcium measurements in ... [more ▼]

In this study, we mutated the four highly conserved intracellular tyrosine residues of the P2X(1) ion channel were mutated into phenylalanine. Simultaneous electrophysiological and calcium measurements in transfected human embryonic kidney (HEK 293) cells indicated that Y362F and Y370F mutants were non-functional, despite their proper plasma membrane expression. The Y16F and Y363F mutants retained 2.2% and 26% of the wild-type P2X(1) activity, respectively. However, no tyrosine phosphorylation was detected on Western blots of P2X(1) immunoprecipitates derived either from HEK 293 cell lysates or from human platelets, expressing P2X(1) endogenously. Thus, Y16, Y362, Y363 and Y370 are required for the appropriate three-dimensional structure and function of the intracellular P2X(1) domains. [less ▲]

P2X1-mediated activation of Ca2+-calmodulin leads to myosin light chain and ERK2 phosphorylation in human platelets.

in Haematologica (2002), 87

Enhanced Platelet Reactivity to Collagen and Shear Stress in Transgenic Mice Overexpressing the Platelet P2X1 Ion Channel

in Blood (2002), 100

P2X(1)-mediated activation of extracellular signal-regulated kinase 2 contributes to platelet secretion and aggregation induced by collagen.

in Blood (2002)

This study shows that mild platelet stimulation with collagen rapidly releases ATP, which activates the P2X(1)-PKC-ERK2 pathway. This process enhances further degranulation of the collagen-primed granules ... [more ▼]

This study shows that mild platelet stimulation with collagen rapidly releases ATP, which activates the P2X(1)-PKC-ERK2 pathway. This process enhances further degranulation of the collagen-primed granules allowing platelet aggregation to be completed. [less ▲]

Rapid Ca2+ influx via the platelet P2X1 ion channel requires its N- and C-terminal tyrosine phosphorylation.

in Thrombosis and Haemostasis (2001)

The ATP-gated P2X1 ion channel acts as a positive regulator of platelet responses to collagen.

in Thrombosis and Haemostasis (2001)

This study shows that, during collagen-initiated platelet activation, the early secretion of ATP results in the activation of the P2X1 ion channel, which plays a role as a positive regulator of further ... [more ▼]

This study shows that, during collagen-initiated platelet activation, the early secretion of ATP results in the activation of the P2X1 ion channel, which plays a role as a positive regulator of further platelet responses. [less ▲]

A natural dominant negative P2X1 receptor due to deletion of a single amino acid residue.

in Journal of Biological Chemistry (2000)

We describe a naturally occurring dominant negative P2X1 mutant. This mutant lacks one leucine within a stretch of four leucine residues in its second transmembrane domain (TM2) (amino acids 351-354 ... [more ▼]

We describe a naturally occurring dominant negative P2X1 mutant. This mutant lacks one leucine within a stretch of four leucine residues in its second transmembrane domain (TM2) (amino acids 351-354). Confocal microscopy revealed proper plasma membrane localization of the mutant in stably transfected HEK293 cells. Nevertheless, voltage-clamped HEK293 cells expressing mutated P2X1 channels failed to develop an ATP or ADP-induced current. Furthermore, when co-expressed with the wild type receptor in Xenopus oocytes, the mutated protein exhibited a dose-dependent dominant negative effect on the normal ATP or ADP-induced P2X1 channel activity. These data indicate that deletion of a single apolar amino acid residue at the inner border of the P2X1 TM2 generates a nonfunctional channel. [less ▲]