| Id |
Subject |
Object |
Predicate |
Lexical cue |
| T1 |
0-116 |
Sentence |
denotes |
Genuine monovalent ligands of TrkA nerve growth factor receptors reveal a novel pharmacological mechanism of action. |
| T2 |
117-275 |
Sentence |
denotes |
Developing small molecule agonistic ligands for tyrosine kinase receptors has been difficult, and it is generally thought that such ligands require bivalency. |
| T3 |
276-455 |
Sentence |
denotes |
Moreover, multisubunit receptors are difficult to target, because each subunit contributes to ligand affinity, and each subunit may have distinct and sometimes opposing functions. |
| T4 |
456-628 |
Sentence |
denotes |
Here, the nerve growth factor receptor subunits p75 and the tyrosine kinase TrkA were studied using artificial ligands that bind specifically to their extracellular domain. |
| T5 |
629-673 |
Sentence |
denotes |
Bivalent TrkA ligands afford robust signals. |
| T6 |
674-898 |
Sentence |
denotes |
However, genuine monomeric and monovalent TrkA ligands afford partial agonism, activate the tyrosine kinase activity, cause receptor internalization, and induce survival and differentiation in cell lines and primary neurons. |
| T7 |
899-990 |
Sentence |
denotes |
Monomeric and monovalent TrkA ligands can synergize with ligands that bind the p75 subunit. |
| T8 |
991-1095 |
Sentence |
denotes |
However, the p75 ligands used in this study must be bivalent, and monovalent p75 ligands have no effect. |
| T9 |
1096-1349 |
Sentence |
denotes |
These findings will be useful in designing and developing screens of small molecules selective for tyrosine kinase receptors and indicate that strategies for designing agonists of multisubunit receptors require consideration of the role of each subunit. |
| T10 |
1350-1530 |
Sentence |
denotes |
Last, the strategy of using anti-receptor mAbs and small molecule hormone mimics as receptor ligands could be applied to the study of many other heteromeric cell surface receptors. |
