Analyzing the mechanism of Rap1 activation in platelets: Rap1 activation is related to the release reaction mediated through the collagen receptor GPVI

被引:8
|
作者
Jung, Stephanie M.
Ohnuma, Masaaki
Watanabe, Naohide
Sonoda, Mamiko
Handa, Makoto
Moroi, Masaaki [1 ]
机构
[1] Kurume Univ, Inst Life Sci, Dept Prot Biochem, Kurume, Fukuoka 8390864, Japan
[2] Keio Univ, Sch Med, Dept Internal Med, Div Hematol,Blood Ctr, Tokyo 1608582, Japan
关键词
Rap1; platelets; GPVI; integrin activation; release reaction;
D O I
10.1016/j.thromres.2005.11.002
中图分类号
R5 [内科学];
学科分类号
1002 ; 100201 ;
摘要
The abundant Rap1 in platelets becomes activated when these cells are stimulated by various agonists, but its function has remained unknown. In view of this, we developed an assay to quantitatively measure activated Rap1 and used it to determine relationships between Rap1 activation and several platelet functions: integrin alpha(2)beta(1) activation, tyrosine phosphorylation, and the release reaction. We looked at how these processes are affected by the protein kinase C inhibitor BIMI, tyrosine kinase inhibitor PP2, PI 3-kinase inhibitor wortmannin, and ADP scavenger apyrase. In CRP (collagen related peptide)-activated platelets, all the inhibitors severely inhibited Rapl activation, but had little effect on integrin alpha(2)beta(1) activation, indicating that the integrin activation mechanism is different from the Rapl activation mechanism, at least in GPVI-dependent activation. With p85 alpha-null mouse platelets, we demonstrated that Rap1 activation involves PI 3-kinase p85 alpha-dependent tyrosine phosphorylation. All the inhibitors similarly decreased Rap1 activation and the serotonin release reaction, and the inhibition of Rap1 activation was not due to the lack of released ADP. Our results indicate that platelet Rap1 activation is closely related to the release reaction and not to integrin alpha(2)beta(1) activation in GPVI-mediated platelet activation. (c) 2005 Elsevier Ltd. All rights reserved.
引用
收藏
页码:509 / 521
页数:13
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