| Id |
Subject |
Object |
Predicate |
Lexical cue |
| T1 |
0-89 |
Sentence |
denotes |
Noncatalytic function of ERK1/2 can promote Raf/MEK/ERK-mediated growth arrest signaling. |
| T2 |
90-156 |
Sentence |
denotes |
Kinase activity is known as the key biochemical property of MAPKs. |
| T3 |
157-265 |
Sentence |
denotes |
Here, we report that ERK1/2 also utilizes its noncatalytic function to mediate certain signal transductions. |
| T4 |
266-603 |
Sentence |
denotes |
Sustained activation of the Raf/MEK/ERK pathway induces growth arrest, accompanied by changes in cell cycle regulators (decreased retinoblastoma phosphorylation, E2F1 down-regulation, and/or p21(CIP1) up-regulation) and cell type-specific changes in morphology and expression of c-Myc or RET in the human tumor lines LNCaP, U251, and TT. |
| T5 |
604-671 |
Sentence |
denotes |
Ablation of ERK1/2 by RNA interference abrogated all these effects. |
| T6 |
672-1064 |
Sentence |
denotes |
However, active site-disabled ERK mutants (ERK1-K71R, ERK2-K52R, and ERK2-D147A), which competitively inhibit activation of endogenous ERK1/2, could not block Raf/MEK-induced growth arrest as well as changes in the cell cycle regulators, although they effectively blocked phosphorylation of the ERK1/2 catalytic activity readouts, p90(RSK) and ELK1, as well as the cell type-specific changes. |
| T7 |
1065-1410 |
Sentence |
denotes |
Because this indicated a potential noncatalytic ERK1/2 function, we generated stable lines of the tumor cells in which both ERK1 and ERK2 were significantly knocked down, and we further investigated the possibility using rat-derived kinase-deficient ERK mutants (ERK2-K52R and ERK2-T183A/Y185F) that were not targeted by human small hairpin RNA. |
| T8 |
1411-1664 |
Sentence |
denotes |
Indeed, ERK2-K52R selectively restored Raf-induced growth inhibitory signaling in ERK1/2-depleted cells, as manifested by regained cellular ability to undergo growth arrest and to control the cell cycle regulators without affecting c-Myc and morphology. |
| T9 |
1665-1766 |
Sentence |
denotes |
However, ERK2-T183A/Y185F was less effective, indicating the requirement of TEY site phosphorylation. |
| T10 |
1767-1920 |
Sentence |
denotes |
Our study suggests that functions of ERK1/2 other than its "canonical" kinase activity are also involved in the pathway-mediated growth arrest signaling. |
