| + |
NEDD4L | up-regulates activity 
ubiquitination
|
NF2 |
0.263 |
| Identifier |
Residue |
Sequence |
Organism |
Cell Line |
| SIGNOR-263662 |
Lys396 |
QITEEEAkLLAQKAA |
Homo sapiens |
|
| pmid |
sentence |
| 33058421 |
Merlin ubiquitination is mediated by the E3 ubiquitin ligase, NEDD4L, which requires a scaffold protein, AMOTL1, to approach Merlin. Several NF2-patient-derived Merlin mutations disrupt its binding to AMOTL1 and its regulation by the AMOTL1-NEDD4L apparatus. Lysine (K) 396 is the major ubiquitin conjugation residue. Disruption of Merlin ubiquitination by the K396R mutation or NEDD4L depletion diminishes its binding to Lats1 and inhibits Lats1 activation. These effects are also accompanied by loss of Merlin's anti-mitogenic and tumor suppressive properties. Thus, we propose that dephosphorylation and ubiquitination compose an intramolecular relay to activate Merlin functions in activating the Hippo pathway during growth control. |
|
| Publications: |
1 |
Organism: |
Homo Sapiens |
| Pathways: | Hippo Signaling |
| + |
PRKACA | up-regulates
phosphorylation
|
NF2 |
0.389 |
| Identifier |
Residue |
Sequence |
Organism |
Cell Line |
| SIGNOR-159840 |
Ser10 |
GAIASRMsFSSLKRK |
Homo sapiens |
|
| pmid |
sentence |
| 18071304 |
Merlin contains a c-terminal serine 518, which is phosphorylated both by p21-activated kinase (pak) and protein kinase a (pka) (shaw et al., 2001;kissil et al., 2002;xiao et al., 2002;alfthan et al., 2004). Phosphorylation at this site is predicted to result in a more open conformation incapable of inhibiting cell growth, |
|
| Publications: |
1 |
Organism: |
Homo Sapiens |
| + |
TNIK | up-regulates activity
phosphorylation
|
NF2 |
0.2 |
| Identifier |
Residue |
Sequence |
Organism |
Cell Line |
| SIGNOR-278388 |
Ser13 |
ASRMSFSsLKRKQPK |
Homo sapiens |
|
| pmid |
sentence |
| 33495197 |
Consistently with TNIK modulating Merlin, we also observed reduced YAP levels following TNIK knockdown in LK2 and NCI-H520 cells (Supplementary Fig. S7B).|Using in vitro kinase assays followed by phosphopeptide mapping, and mass spectrometry analysis on Merlin isolated from cells co-expressing TNIK and Merlin, we determined that TNIK could phosphorylate Merlin at S13, T272, S315, and T576 (Fig. 4B, Supplementary Fig. S4D, and Supplementary Table S3). |
|
| Identifier |
Residue |
Sequence |
Organism |
Cell Line |
| SIGNOR-278387 |
Ser315 |
MRRRKADsLEVQQMK |
Homo sapiens |
|
| pmid |
sentence |
| 33495197 |
Consistently with TNIK modulating Merlin, we also observed reduced YAP levels following TNIK knockdown in LK2 and NCI-H520 cells (Supplementary Fig. S7B).|Using in vitro kinase assays followed by phosphopeptide mapping, and mass spectrometry analysis on Merlin isolated from cells co-expressing TNIK and Merlin, we determined that TNIK could phosphorylate Merlin at S13, T272, S315, and T576 (Fig. 4B, Supplementary Fig. S4D, and Supplementary Table S3). |
|
| Identifier |
Residue |
Sequence |
Organism |
Cell Line |
| SIGNOR-278386 |
Thr272 |
SYSDKEFtIKPLDKK |
Homo sapiens |
|
| pmid |
sentence |
| 33495197 |
Consistently with TNIK modulating Merlin, we also observed reduced YAP levels following TNIK knockdown in LK2 and NCI-H520 cells (Supplementary Fig. S7B).|Using in vitro kinase assays followed by phosphopeptide mapping, and mass spectrometry analysis on Merlin isolated from cells co-expressing TNIK and Merlin, we determined that TNIK could phosphorylate Merlin at S13, T272, S315, and T576 (Fig. 4B, Supplementary Fig. S4D, and Supplementary Table S3). |
|
| Identifier |
Residue |
Sequence |
Organism |
Cell Line |
| SIGNOR-278385 |
Thr576 |
GGSSKHNtIKKLTLQ |
Homo sapiens |
|
| pmid |
sentence |
| 33495197 |
Consistently with TNIK modulating Merlin, we also observed reduced YAP levels following TNIK knockdown in LK2 and NCI-H520 cells (Supplementary Fig. S7B).|Using in vitro kinase assays followed by phosphopeptide mapping, and mass spectrometry analysis on Merlin isolated from cells co-expressing TNIK and Merlin, we determined that TNIK could phosphorylate Merlin at S13, T272, S315, and T576 (Fig. 4B, Supplementary Fig. S4D, and Supplementary Table S3). |
|
| Publications: |
4 |
Organism: |
Homo Sapiens |
| + |
PAK1 | down-regulates 
phosphorylation
|
NF2 |
0.636 |
| Identifier |
Residue |
Sequence |
Organism |
Cell Line |
| SIGNOR-159764 |
Ser518 |
DTDMKRLsMEIEKEK |
Homo sapiens |
|
| pmid |
sentence |
| 18071304 |
Merlin contains a c-terminal serine 518, which is phosphorylated both by p21-activated kinase (pak) and protein kinase a (pka) (shaw et al., 2001;kissil et al., 2002;xiao et al., 2002;alfthan et al., 2004). Phosphorylation at this site is predicted to result in a more open conformation incapable of inhibiting cell growth, |
|
| Publications: |
1 |
Organism: |
Homo Sapiens |
| + |
PPP1CB | up-regulates
dephosphorylation
|
NF2 |
0.383 |
| Identifier |
Residue |
Sequence |
Organism |
Cell Line |
| SIGNOR-159836 |
Ser518 |
DTDMKRLsMEIEKEK |
Homo sapiens |
|
| pmid |
sentence |
| 18071304 |
When serine 518 is dephosphorylated by the myosin phosphatase mypt-1-pp1?, The tumor suppressor function of merlin is activated, inhibiting the ras signaling pathway and leading to growth arrest |
|
| Publications: |
1 |
Organism: |
Homo Sapiens |
| + |
PRKACA | down-regulates
phosphorylation
|
NF2 |
0.389 |
| Identifier |
Residue |
Sequence |
Organism |
Cell Line |
| SIGNOR-159844 |
Ser518 |
DTDMKRLsMEIEKEK |
Homo sapiens |
|
| pmid |
sentence |
| 18071304 |
Merlin localizes to the cell membrane where it links the actin cytoskeleton to membrane proteins.we identify a novel pka phosphorylation site, serine 10, in the n terminus of merlin. s10a reduces the amount of cellular f-actin and merlin s10d stabilizes f-actin filaments. |
|
| Publications: |
1 |
Organism: |
Homo Sapiens |
| + |
PAK2 | down-regulates
phosphorylation
|
NF2 |
0.499 |
| Identifier |
Residue |
Sequence |
Organism |
Cell Line |
| SIGNOR-159768 |
Ser518 |
DTDMKRLsMEIEKEK |
Homo sapiens |
|
| pmid |
sentence |
| 18071304 |
Merlin contains a c-terminal serine 518, which is phosphorylated both by p21-activated kinase (pak) and protein kinase a (pka) (shaw et al., 2001;kissil et al., 2002;xiao et al., 2002;alfthan et al., 2004). Phosphorylation at this site is predicted to result in a more open conformation incapable of inhibiting cell growth, |
|
| Publications: |
1 |
Organism: |
Homo Sapiens |
| + |
NF2 | up-regulates
binding
|
LATS1 |
0.703 |
| Identifier |
Residue |
Sequence |
Organism |
Cell Line |
| SIGNOR-202604 |
|
|
Homo sapiens |
|
| pmid |
sentence |
| 24012335 |
As expected, the nf2-/- fc-912 cells were defective in lats1/2 phosphorylation (figure s2e-f). Subcellular fractionation revealed a significant increase of endogenous lats1/2 in the cytoplasmic relative to the membrane fraction in the nf2-/- fc-912 schwann cells compared to the nf2+/+ fh-912 schwann cells (figure 2e). This localization defect was rescued by re-expression of nf2 |
|
| Publications: |
1 |
Organism: |
Homo Sapiens |
| Pathways: | Hippo Signaling |
| + |
NF2 | up-regulates activity
binding
|
STK3/4 |
0.418 |
| Identifier |
Residue |
Sequence |
Organism |
Cell Line |
| SIGNOR-269948 |
|
|
Mus musculus |
Cardiomyocyte Cell Line |
| pmid |
sentence |
| 27402866 |
NF2 is activated by oxidative stress in cardiomyocytes and mouse myocardium and facilitates apoptosis. NF2 promotes I/R injury through activation of Mst1 and inhibition of Yap, thereby regulating Hippo signaling in the adult heart. |
|
| Publications: |
1 |
Organism: |
Mus Musculus |
| Pathways: | Hippo Signaling |
| + |
NF2 | up-regulates activity
binding
|
LATS1/2 |
0.751 |
| Identifier |
Residue |
Sequence |
Organism |
Cell Line |
| SIGNOR-263663 |
|
|
Homo sapiens |
|
| pmid |
sentence |
| 33058421 |
The Hippo pathway tumor suppressor Merlin/NF2 is known to be regulated by phosphorylation. Here, the E3 ubiquitin ligase NEDD4L is shown to promote Hippo pathway activation via ubiquitination of Merlin. |
|
| Publications: |
1 |
Organism: |
Homo Sapiens |
| Pathways: | Hippo Signaling |
| + |
Cullin4-RBX1-DDB1 | down-regulates quantity by destabilization
polyubiquitination
|
NF2 |
0.331 |
| Identifier |
Residue |
Sequence |
Organism |
Cell Line |
| SIGNOR-271674 |
|
|
Homo sapiens |
HEK-293 Cell |
| pmid |
sentence |
| 18332868 |
VprBP targets Merlin to the Roc1-Cul4A-DDB1 E3 ligase complex for degradation. In this study, we provide evidence to show that Merlin is regulated in a Roc1-Cullin4A-DDB1-dependent manner. Following serum stimulation, Merlin is recruited to the E3 ligase complex through a direct interaction with the WD40-containing adaptor protein VprBP. Loading of Merlin to the E3 ubiquitin ligase complex resulted in its polyubiquitination, and consequently its proteasome-mediated degradation. |
|
| Publications: |
1 |
Organism: |
Homo Sapiens |
| + |
DCAF1 | down-regulates quantity by destabilization
binding
|
NF2 |
0.2 |
| Identifier |
Residue |
Sequence |
Organism |
Cell Line |
| SIGNOR-271673 |
|
|
Homo sapiens |
HEK-293 Cell |
| pmid |
sentence |
| 18332868 |
VprBP targets Merlin to the Roc1-Cul4A-DDB1 E3 ligase complex for degradation. In this study, we provide evidence to show that Merlin is regulated in a Roc1-Cullin4A-DDB1-dependent manner. Following serum stimulation, Merlin is recruited to the E3 ligase complex through a direct interaction with the WD40-containing adaptor protein VprBP. Loading of Merlin to the E3 ubiquitin ligase complex resulted in its polyubiquitination, and consequently its proteasome-mediated degradation. |
|
| Publications: |
1 |
Organism: |
Homo Sapiens |
| + |
NF2 | up-regulates
binding
|
LATS2 |
0.707 |
| Identifier |
Residue |
Sequence |
Organism |
Cell Line |
| SIGNOR-202607 |
|
|
Homo sapiens |
|
| pmid |
sentence |
| 24012335 |
As expected, the nf2-/- fc-912 cells were defective in lats1/2 phosphorylation (figure s2e-f). Subcellular fractionation revealed a significant increase of endogenous lats1/2 in the cytoplasmic relative to the membrane fraction in the nf2-/- fc-912 schwann cells compared to the nf2+/+ fh-912 schwann cells (figure 2e). This localization defect was rescued by re-expression of nf2 |
|
| Publications: |
1 |
Organism: |
Homo Sapiens |
| Pathways: | Hippo Signaling |
| + |
NF2 | up-regulates activity
binding
|
STK3 |
0.331 |
| Identifier |
Residue |
Sequence |
Organism |
Cell Line |
| SIGNOR-261955 |
|
|
Mus musculus |
Cardiomyocyte Cell Line |
| pmid |
sentence |
| 27402866 |
NF2 is activated by oxidative stress in cardiomyocytes and mouse myocardium and facilitates apoptosis. NF2 promotes I/R injury through activation of Mst1 and inhibition of Yap, thereby regulating Hippo signaling in the adult heart. |
|
| Publications: |
1 |
Organism: |
Mus Musculus |
| Pathways: | Hippo Signaling |
| + |
NF2 | up-regulates activity
binding
|
STK4 |
0.418 |
| Identifier |
Residue |
Sequence |
Organism |
Cell Line |
| SIGNOR-261956 |
|
|
Mus musculus |
Cardiomyocyte Cell Line |
| pmid |
sentence |
| 27402866 |
NF2 is activated by oxidative stress in cardiomyocytes and mouse myocardium and facilitates apoptosis. NF2 promotes I/R injury through activation of Mst1 and inhibition of Yap, thereby regulating Hippo signaling in the adult heart. |
|
| Publications: |
1 |
Organism: |
Mus Musculus |
| Pathways: | Hippo Signaling |
| + |
PAK | down-regulates
phosphorylation
|
NF2 |
0.2 |
| Identifier |
Residue |
Sequence |
Organism |
Cell Line |
| SIGNOR-269976 |
|
|
Homo sapiens |
|
| pmid |
sentence |
| 18071304 |
Merlin contains a c-terminal serine 518, which is phosphorylated both by p21-activated kinase (pak) and protein kinase a (pka) (shaw et al., 2001;kissil et al., 2002;xiao et al., 2002;alfthan et al., 2004). Phosphorylation at this site is predicted to result in a more open conformation incapable of inhibiting cell growth, |
|
| Publications: |
1 |
Organism: |
Homo Sapiens |
3.0
NF2
- 
- 