Id |
Subject |
Object |
Predicate |
Lexical cue |
T1 |
0-132 |
Sentence |
denotes |
Extracellular signal-regulated kinase (ERK) phosphorylates histone deacetylase 6 (HDAC6) at serine 1035 to stimulate cell migration. |
T2 |
133-289 |
Sentence |
denotes |
Histone deacetylase 6 (HDAC6) is well known for its ability to promote cell migration through deacetylation of its cytoplasmic substrates such as α-tubulin. |
T3 |
290-370 |
Sentence |
denotes |
However, how HDAC6 itself is regulated to control cell motility remains elusive. |
T4 |
371-518 |
Sentence |
denotes |
Previous studies have shown that one third of extracellular signal-regulated kinase (ERK) is associated with the microtubule cytoskeleton in cells. |
T5 |
519-580 |
Sentence |
denotes |
Yet, no connection between HDAC6 and ERK has been discovered. |
T6 |
581-717 |
Sentence |
denotes |
Here, for the first time, we reveal that ERK binds to and phosphorylates HDAC6 to promote cell migration via deacetylation of α-tubulin. |
T7 |
718-823 |
Sentence |
denotes |
We have identified two novel ERK-mediated phosphorylation sites: threonine 1031 and serine 1035 in HDAC6. |
T8 |
824-989 |
Sentence |
denotes |
Both sites were phosphorylated by ERK1 in vitro, whereas Ser-1035 was phosphorylated in response to the activation of EGFR-Ras-Raf-MEK-ERK signaling pathway in vivo. |
T9 |
990-1172 |
Sentence |
denotes |
HDAC6-null mouse embryonic fibroblasts rescued by the nonphosphorylation mimicking mutant displayed significantly reduced cell migration compared with those rescued by the wild type. |
T10 |
1173-1306 |
Sentence |
denotes |
Consistently, the nonphosphorylation mimicking mutant exerted lower tubulin deacetylase activity in vivo compared with the wild type. |
T11 |
1307-1403 |
Sentence |
denotes |
These data indicate that ERK/HDAC6-mediated cell motility is through deacetylation of α-tubulin. |
T12 |
1404-1520 |
Sentence |
denotes |
Overall, our results suggest that HDAC6-mediated cell migration could be governed by EGFR-Ras-Raf-MEK-ERK signaling. |