Id |
Subject |
Object |
Predicate |
Lexical cue |
T1 |
0-149 |
Sentence |
denotes |
Tyr728 in the kinase domain of the murine kinase suppressor of RAS 1 regulates binding and activation of the mitogen-activated protein kinase kinase. |
T2 |
150-237 |
Sentence |
denotes |
In metazoans, the highly conserved MAPK signaling pathway regulates cell fate decision. |
T3 |
238-353 |
Sentence |
denotes |
Aberrant activation of this pathway has been implicated in multiple human cancers and some developmental disorders. |
T4 |
354-515 |
Sentence |
denotes |
KSR1 functions as an essential scaffold that binds the individual components of the cascade and coordinates their assembly into multiprotein signaling platforms. |
T5 |
516-597 |
Sentence |
denotes |
The mechanism of KSR1 regulation is highly complex and not completely understood. |
T6 |
598-687 |
Sentence |
denotes |
In this study, we identified Tyr(728) as a novel regulatory phosphorylation site in KSR1. |
T7 |
688-820 |
Sentence |
denotes |
We show that Tyr(728) is phosphorylated by LCK, uncovering an additional and unexpected link between Src kinases and MAPK signaling. |
T8 |
821-979 |
Sentence |
denotes |
To understand how phosphorylation of Tyr(728) may regulate the role of KSR1 in signal transduction, we integrated structural modeling and biochemical studies. |
T9 |
980-1107 |
Sentence |
denotes |
We demonstrate that Tyr(728) is involved in maintaining the conformation of the KSR1 kinase domain required for binding to MEK. |
T10 |
1108-1224 |
Sentence |
denotes |
It also affects phosphorylation and activation of MEK by RAF kinases and consequently influences cell proliferation. |
T11 |
1225-1337 |
Sentence |
denotes |
Moreover, our studies suggest that phosphorylation of Tyr(728) may affect the intrinsic kinase activity of KSR1. |
T12 |
1338-1543 |
Sentence |
denotes |
Together, we propose that phosphorylation of Tyr(728) may regulate the transition between the scaffolding and the catalytic function of KSR1 serving as a control point used to fine-tune cellular responses. |