| Id |
Subject |
Object |
Predicate |
Lexical cue |
| T1 |
0-139 |
Sentence |
denotes |
Distinct pathways regulate Syk protein activation downstream of immune tyrosine activation motif (ITAM) and hemITAM receptors in platelets. |
| T2 |
140-232 |
Sentence |
denotes |
Tyrosine kinase pathways are known to play an important role in the activation of platelets. |
| T3 |
233-406 |
Sentence |
denotes |
In particular, the GPVI and CLEC-2 receptors are known to activate Syk upon tyrosine phosphorylation of an immune tyrosine activation motif (ITAM) and hemITAM, respectively. |
| T4 |
407-510 |
Sentence |
denotes |
However, unlike GPVI, the CLEC-2 receptor contains only one tyrosine motif in the intracellular domain. |
| T5 |
511-593 |
Sentence |
denotes |
The mechanisms by which this receptor activates Syk are not completely understood. |
| T6 |
594-685 |
Sentence |
denotes |
In this study, we identified a novel signaling mechanism in CLEC-2-mediated Syk activation. |
| T7 |
686-872 |
Sentence |
denotes |
CLEC-2-mediated, but not GPVI-mediated, platelet activation and Syk phosphorylation were abolished by inhibition of PI3K, which demonstrates that PI3K regulates Syk downstream of CLEC-2. |
| T8 |
873-1023 |
Sentence |
denotes |
Ibrutinib, a Tec family kinase inhibitor, also completely abolished CLEC-2-mediated aggregation and Syk phosphorylation in human and murine platelets. |
| T9 |
1024-1207 |
Sentence |
denotes |
Furthermore, embryos lacking both Btk and Tec exhibited cutaneous edema associated with blood-filled vessels in a typical lymphatic pattern similar to CLEC-2 or Syk-deficient embryos. |
| T10 |
1208-1401 |
Sentence |
denotes |
Thus, our data show, for the first time, that PI3K and Tec family kinases play a crucial role in the regulation of platelet activation and Syk phosphorylation downstream of the CLEC-2 receptor. |
