| Id |
Subject |
Object |
Predicate |
Lexical cue |
| T1 |
0-140 |
Sentence |
denotes |
The Cbl phosphotyrosine-binding domain selects a D(N/D)XpY motif and binds to the Tyr292 negative regulatory phosphorylation site of ZAP-70. |
| T2 |
141-298 |
Sentence |
denotes |
The Cbl protooncogene product has emerged as a novel negative regulator of receptor and non-receptor tyrosine kinases through currently undefined mechanisms. |
| T3 |
299-400 |
Sentence |
denotes |
Therefore, determining how Cbl physically interacts with tyrosine kinases is of substantial interest. |
| T4 |
401-586 |
Sentence |
denotes |
We recently identified a phosphotyrosine binding (PTB) domain residing within the N-terminal transforming region of Cbl (Cbl-N), which mediated direct binding to ZAP-70 tyrosine kinase. |
| T5 |
587-804 |
Sentence |
denotes |
Here, we have screened a degenerate phosphopeptide library and show that the Cbl-PTB domain selects a D(N/D)XpY motif, reminiscent of but distinct from the NPXpY motif recognized by the PTB domains of Shc and IRS-1/2. |
| T6 |
805-992 |
Sentence |
denotes |
A phosphopeptide predicted by this motif and corresponding to the in vivo negative regulatory phosphorylation site of ZAP-70 (Tyr(P)292) specifically inhibited binding of ZAP-70 to Cbl-N. |
| T7 |
993-1189 |
Sentence |
denotes |
A ZAP-70/Y292F mutant failed to bind to Cbl-N, whereas a D290A mutant resulted in a 64% decrease in binding, confirming the importance of the Tyr(P) and Y-2 residues in Cbl-PTB domain recognition. |
| T8 |
1190-1285 |
Sentence |
denotes |
Finally the ZAP-70/Y292F mutant also failed to associate with Cbl-N or full-length Cbl in vivo. |
| T9 |
1286-1508 |
Sentence |
denotes |
These results identify a potential Cbl-PTB domain-dependent role for Cbl in the negative regulation of ZAP-70 and predict potential Cbl-PTB domain binding sites on other protein tyrosine kinases known to interact with Cbl. |
