| Id |
Subject |
Object |
Predicate |
Lexical cue |
| T1 |
0-104 |
Sentence |
denotes |
A novel PDZ domain containing guanine nucleotide exchange factor links heterotrimeric G proteins to Rho. |
| T2 |
105-194 |
Sentence |
denotes |
Small GTP-binding proteins of the Rho family play a critical role in signal transduction. |
| T3 |
195-296 |
Sentence |
denotes |
However, there is still very limited information on how they are activated by cell surface receptors. |
| T4 |
297-562 |
Sentence |
denotes |
Here, we used a consensus sequence for Dbl domains of Rho guanine nucleotide exchange factors (GEFs) to search DNA data bases, and identified a novel human GEF for Rho-related GTPases harboring structural features indicative of its possible regulatory mechanism(s). |
| T5 |
563-802 |
Sentence |
denotes |
This protein contained a tandem DH/PH domain closely related to those of Rho-specific GEFs, a PDZ domain, a proline-rich domain, and an area of homology to Lsc, p115-RhoGEF, and a Drosophila RhoGEF that was termed Lsc-homology (LH) domain. |
| T6 |
803-980 |
Sentence |
denotes |
This novel molecule, designated PDZ-RhoGEF, activated biological and biochemical pathways specific for Rho, and activation of these pathways required an intact DH and PH domain. |
| T7 |
981-1150 |
Sentence |
denotes |
However, the PDZ domain was dispensable for these functions, and mutants lacking the LH domain were more active, suggesting a negative regulatory role for the LH domain. |
| T8 |
1151-1348 |
Sentence |
denotes |
A search for additional molecules exhibiting an LH domain revealed a limited homology with the catalytic region of a newly identified GTPase-activating protein for heterotrimeric G proteins, RGS14. |
| T9 |
1349-1468 |
Sentence |
denotes |
This prompted us to investigate whether PDZ-RhoGEF could interact with representative members of each G protein family. |
| T10 |
1469-1658 |
Sentence |
denotes |
We found that PDZ-RhoGEF was able to form, in vivo, stable complexes with two members of the Galpha12 family, Galpha12 and Galpha13, and that this interaction was mediated by the LH domain. |
| T11 |
1659-1776 |
Sentence |
denotes |
Furthermore, we obtained evidence to suggest that PDZ-RhoGEF mediates the activation of Rho by Galpha12 and Galpha13. |
| T12 |
1777-2105 |
Sentence |
denotes |
Together, these findings suggest the existence of a novel mechanism whereby the large family of cell surface receptors that transmit signals through heterotrimeric G proteins activate Rho-dependent pathways: by stimulating the activity of members of the Galpha12 family which, in turn, activate an exchange factor acting on Rho. |