| Id |
Subject |
Object |
Predicate |
Lexical cue |
| T1 |
0-135 |
Sentence |
denotes |
Csk homologous kinase (CHK) and ErbB-2 interactions are directly coupled with CHK negative growth regulatory function in breast cancer. |
| T2 |
136-394 |
Sentence |
denotes |
Our previous studies demonstrated that Csk homologous kinase (CHK) acts as a negative growth regulator of human breast cancer through inhibition of ErbB-2/neu-mediated Src family kinase activity (Bougeret, C., Jiang, S., Keydar, I., and Avraham, H. (2001) J. |
| T3 |
395-400 |
Sentence |
denotes |
Biol. |
| T4 |
401-406 |
Sentence |
denotes |
Chem. |
| T5 |
407-424 |
Sentence |
denotes |
276, 33711-33720. |
| T6 |
425-568 |
Sentence |
denotes |
The interaction between the CHK SH2 domain and Tyr(P)(1248) of the ErbB-2 receptor has been shown to be specific and critical for CHK function. |
| T7 |
569-740 |
Sentence |
denotes |
In this report, we investigated whether the interaction of the CHK SH2 domain and ErbB-2 is directly related to the inhibition of heregulin-stimulated Src kinase activity. |
| T8 |
741-877 |
Sentence |
denotes |
We constructed three CHK SH2 domain binding mutants: G129R (enhanced binding), R147K (inhibited binding), and R147A (disrupted binding). |
| T9 |
878-1010 |
Sentence |
denotes |
NMR spectra for the domains of each construct were used to evaluate their interaction with a Tyr(P)(1248)-containing ErbB-2 peptide. |
| T10 |
1011-1102 |
Sentence |
denotes |
G129R showed enhanced binding to ErbB-2, whereas binding was completely disrupted by R147A. |
| T11 |
1103-1290 |
Sentence |
denotes |
The enhanced binding mutant showed chemical shift changes at the same residues as wild-type CHK, indicating that this mutant has the same binding characteristics as the wild-type protein. |
| T12 |
1291-1471 |
Sentence |
denotes |
Furthermore, inhibition of heregulin-stimulated Src kinase activity was markedly diminished by R147A, whereas G129R-mediated inhibition was stronger as compared with wild-type CHK. |
| T13 |
1472-1629 |
Sentence |
denotes |
These results indicate that the specific interaction of CHK and ErbB-2 via the SH2 domain of CHK is directly related to the growth inhibitory effects of CHK. |
| T14 |
1630-1801 |
Sentence |
denotes |
These new CHK high affinity binding constructs may serve as good candidates for inhibition of the ErbB-2/Src transduction pathway in gene therapy studies in breast cancer. |
