GleghornLab/Signor_3class · Datasets at Hugging Face

IdA stringlengths 6 21	IdB stringlengths 6 21	labels int64 0 2	mechanism stringclasses 40 values	effect stringclasses 10 values	score float64 0.1 0.99 ⌀	sentence stringlengths 10 1.63k ⌀	signor_id stringlengths 12 14
Q9Y4K4	P49841	1	phosphorylation	down-regulates	0.2	Gckr can phosphorylate an n-terminal recombinant fusion protein of gsk3_ and enhance the in vivo phosphorylation of gsk3_ on serine 9reduction of gckr expression inhibits wnt3a-induced phosphorylation of gsk3_ at serine 9 and decreases the accumulation of cytosolic _-catenin.	SIGNOR-148908
P15311	Q13464	0	phosphorylation	up-regulates	0.732	Activation of ezrin is mediated by initial pip2 binding and subsequent phosphorylation of threonine 567. We performed an in vitro kinase assay with 80 selected kinases on an ezrin peptide containing the t567 phosphorylation site (figure 3a). In this screen, we identified the mst and rock kinases as the most potent kinases for the ezrin peptide	SIGNOR-185567
P05129	P41594	1	phosphorylation	up-regulates activity	0.415	Thus, we showed that it is phosphorylation of Ser-839, not Thr-840, that is absolutely required for the unique Ca2+ oscillations produced by mGluR5 activation. The Thr-840 residue is important only in that it is permissive for the PKC-dependent phosphorylation of Ser-839.	SIGNOR-249289
Q8IXI1	O60260	0	polyubiquitination	down-regulates quantity by destabilization	0.2	PINK1 phosphorylates Miro, a component of the primary motor/adaptor complex that anchors kinesin to the mitochondrial surface. The phosphorylation of Miro activates proteasomal degradation of Miro in a Parkin-dependent manner.	SIGNOR-272726
Q9Y6D9	P53350	0	phosphorylation	up-regulates activity	0.464	These findings indicate mechanistic roles contributed by protein phosphorylation and Plk1 to the SAC activity of Mad1.Here, we have studied the phosphorylation of Mad1 and mapped using liquid chromatography-tandem mass spectrometry several phosphorylated amino acids in this protein. One phosphorylated residue, Thr680, was characterized to be important for the kinetochore localization of Mad1 and its SAC function.	SIGNOR-276173
O15111	O00141	0	phosphorylation	up-regulates activity	0.26	SGK1 directly phosphorylates IKKalpha at Thr 23 and indirectly activates IKKalpha at Ser 180.\|SGK1 directly phosphorylates IKKalpha at Thr-23 and indirectly activates IKKalpha at Ser-180.	SIGNOR-278987
P01019	P08246	0	cleavage	up-regulates activity	0.275	Cathepsin G, elastase, and proteinase 3 are serine proteinases released by activated neutrophils. Cathepsin G can cleave angiotensinogen to release angiotensin II, but this activity has not been previously reported for elastase or proteinase 3. In this study we show that elastase and proteinase 3 can release angiotensin I from angiotensinogen and release angiotensin II from angiotensin I and angiotensinogen.	SIGNOR-256313
Q9BXW9	Q9NS91	0	ubiquitination	up-regulates activity	0.521	In summary, these findings suggest a model, where Rad18 promotes monoubiquitination of FANCD2, and associates with a functional complex involving Rad51, BRCA2, and FANCD2 in the repair of CPT induced stalled or collapsed forks.\|In this study we focused on the role of Rad18 mediated activation of FANCD2 and its functional relationship with BRCA2 and Rad51 proteins in repair of CPT induced lesions.	SIGNOR-278712
P54764	Q14938	0	transcriptional regulation	up-regulates quantity	0.2	For example, within the NFI targetome, we identified 6 collagen genes, 13 genes encoding potassium channel or glutamate receptor subunits and a range of factors related to axon guidance (e.g. Slit1, Robo1, Epha4, Epha5, Epha8)	SIGNOR-268908
Q8IW41	P25685	1	phosphorylation	up-regulates	0.463	Phosphorylation of heat shock protein 40 (hsp40/dnajb1) by mitogen-activated protein kinase-activated protein kinase 5 (mk5/prak). Mk5 phosphorylates hsp40/dnajb1 in vivo at ser-149 or/and ser-151 and ser-171 in the c-terminal domain of hsp40/dnajb1. Mk5 modestly stimulates the atp hydrolyse activity of hsp40/hsp70 complex and enhances the repression of heat shock factor 1 driven transcription by hsp40/dnajb1.	SIGNOR-203464
P30872	Q03113	2	binding	up-regulates activity	0.25	Here we systematically quantified ligand-induced interactions between 148 GPCRs and all 11 unique G alpha subunit C-termini. For each receptor, we probed chimeric G alpha subunit activation via a transforming growth factor-alpha (TGF alpha) shedding response in HEK293 cells lacking endogenous Gq/11- and G12/13- signaling. \| We defined positive coupling if any member of the subfamily scored LogRAi ≥ -1 and negative coupling if all of the members scored LogRAi < -1 (Figure 3A-B). ROC analysis gives AUC = 0.78 (Figure S4A) when considering high-confidence known coupling data and suggested a threshold of LogRAi ≥ -1.0 for defining true couplings. \| The score associated to this interaction has a LogRAi ≥ -1.0.	SIGNOR-256958
P37231	P45983	0	phosphorylation	down-regulates activity	0.527	The a/b domain of human ppargamma1 was phosphorylated in vivo, and this was abolished either by mutation of serine 84 to alanine (s84a) or coexpression of a phosphoprotein phosphatase. In vitro, this domain was phosphorylated by erk2 and jnk, and this was markedly reduced in the s84a mutant. Thus, phosphorylation of a mitogen-activated protein kinase site in the a/b region of ppargamma inhibits both ligand-independent and ligand-dependent transactivation functions.	SIGNOR-46518
P68400	P27695	1	phosphorylation	up-regulates activity	0.485	Here we demonstrate that APE/Ref-1 is phosphorylated by casein kinase II (CKII). This was shown for both the recombinant APE/Ref-1 protein (Km=0.55 mM) and for APE/Ref-1 expressed in COS cells. Phosphorylation of APE/Ref-1 did not alter the repair activity of the enzyme, whereas it stimulated its redox capability towards AP-1, thus promoting DNA binding activity of AP-1.	SIGNOR-250825
P24941	Q12800	1	phosphorylation	down-regulates	0.2	In vitro, lsf is phosphorylated by cyclin e/cyclin-dependent kinase 2 (cdk2), cyclin c/cdk2, and cyclin c/cdk3, predominantly on s309. Phosphorylation by cyclin c/cyclin-dependent kinase 2 following mitogenic stimulation of murine fibroblasts inhibits transcriptional activity of lsf during g1 progression	SIGNOR-184160
P12931	Q13972	1	phosphorylation	down-regulates activity	0.47	These proximal Src kinases could potentially directly or indirectly phosphorylate Rasgrf-1 upon BCR activation and thereby further increase its GEF activity.	SIGNOR-280133
Q9P2S2	Q14118	2	binding	up-regulates activity	0.262	The DGC is potentially recruited to the postsynaptic membrane though a direct neurexin–dystroglycan interaction and an indirect interaction with NL2 via the synaptic scaffolding protein S-SCAM.	SIGNOR-265460
P25440	Q9ULU4	1	relocalization	up-regulates activity	0.287	ZMYND8 and BRD2 therefore work together to protect H4Ac domains from HDAC activity.\|Further, when BRD2 was depleted, ZMYND8 accumulation was lost (Fig. 2e), indicating that either BRD2, or the underlying H4Ac, is required for ZMYND8 loading.	SIGNOR-262036
Q16539	P17275	1	phosphorylation	up-regulates	0.502	These results clearly demonstrate that phosphorylation by p38 kinase is essential for the regulation of dmp1 transcription by junb and p300. phosphorylation of junb at ser-79 was found to be essential for its interaction with p300.	SIGNOR-127545
P49841	P52945	1	phosphorylation	down-regulates quantity	0.2	We show that glucose levels modulate PDX1 protein phosphorylation at a novel C-terminal GSK3 consensus that maps to serines 268 and 272. A decrease in glucose levels triggers increased turnover of the PDX1 protein in a GSK3-dependent manner, such that PDX1 phosphomutants are refractory to the destabilizing effect of low glucose	SIGNOR-255566
Q14957	P62258	2	binding	up-regulates quantity by stabilization	0.317	Here, we demonstrate that PKB/Akt directly phosphorylates NR2C on serine 1096 (S1096). In addition, we identify 14-3-3epsilon as an NR2C interactor, whose binding is dependent on S1096 phosphorylation. These data are all consistent with a model in which NR1 and NR2C oligomerize, PKB phosphorylates S1096, and 14-3-3ε binds to phosphorylated NR2C thereby promoting NR2C-containing NMDA receptor surface expression in cerebellar granule cells.	SIGNOR-262622
P53671	Q99801	1	phosphorylation	down-regulates activity	0.2	LIMK2 also downregulates NKX3.1 mRNA levels.\|While WT-NKX3.1 was efficiently phosphorylated, the S185A mutant showed no phosphorylation ( xref A), confirming that LIMK2 only phosphorylates the S185 site in NKX3.1.	SIGNOR-278951
O75385	Q8N122	1	phosphorylation	down-regulates activity	0.704	ULK1 phosphorylates RPTOR at S792, S855, and S859.\|When active, ULK1 inhibits MTOR complex 1 through phosphorylation of RPTOR, which has the effect of limiting RPTOR-mediated recruitment of MTOR substrates to MTOR complex 1 [ ].	SIGNOR-278461
P06748	P49450	2	binding	up-regulates activity	0.566	Here we demonstrate that prenucleosomal CENP-A is complexed with histone H4, nucleophosmin 1, and HJURPA minority of NPM1 cofractionated with prenucleosomal CENP-A, consistent with only a small proportion of total NPM1 stably associated with CENP-A. The partial overlap of NPM1 and HJURP with each other supports their formation of distinct prenucleosomal complexes with CENP-A. it is also possible that NPM1 plays a non essential role in the assembly of CENP-A nucleosomes or the nucleophosmin paralogues NPM2 and NPM3 may compensate for the absence of NPM1.	SIGNOR-263708
P25101	P09471	2	binding	up-regulates activity	0.272	Here we systematically quantified ligand-induced interactions between 148 GPCRs and all 11 unique G alpha subunit C-termini. For each receptor, we probed chimeric G alpha subunit activation via a transforming growth factor-alpha (TGF alpha) shedding response in HEK293 cells lacking endogenous Gq/11- and G12/13- signaling. \| We defined positive coupling if any member of the subfamily scored LogRAi ≥ -1 and negative coupling if all of the members scored LogRAi < -1 (Figure 3A-B). ROC analysis gives AUC = 0.78 (Figure S4A) when considering high-confidence known coupling data and suggested a threshold of LogRAi ≥ -1.0 for defining true couplings. \| The score associated to this interaction has a LogRAi ≥ -1.0.	SIGNOR-257253
Q15303	O00329	2	binding	up-regulates	0.395	Pi3k is the sole binding partner to six tyrosines of erbb3 and one in erbb4.	SIGNOR-146885
Q13315	Q96T60	1	phosphorylation	up-regulates	0.462	We demonstrate that pnkp is phosphorylated by the dna-dependent protein kinase (dna-pk) and ataxia-telangiectasia mutated (atm) in vitro. The major phosphorylation site for both kinases was serine 114, with serine 126 being a minor site. Purified pnkp protein with mutation of serines 114 and 126 had decreased dna kinase and dna phosphatase activities and reduced affinity for dna in vitro.	SIGNOR-176008
Q96G74	P68400	0	phosphorylation	up-regulates activity	0.2	Here we show that phosphorylation of the human deubiquitinase DUBA (OTUD5) at a single residue, Ser177, is both necessary and sufficient to activate the enzyme. Treatment with CK2 could activate DUBA purified from E. coli, and this activity was associated with a species monophosphorylated at Ser177 (Fig. 1d).	SIGNOR-265872
P10636-2	P05771	0	phosphorylation	down-regulates activity	0.258	We have studied the relationship between the phosphorylation oftau by several kinases (MARK, PKA, MAPK, GSK3) and its assembly into PHFs. By contrast, MARK and PKA phosphorylate several sites within the repeats (notably theKXGS motifs including Ser262, Ser324, and Ser356, plus Ser320); in addition PKA phosphorylates somesites in the flanking domains, notably Ser214. This type of phosphorylation strongly reduces tau’s affinityfor microtubules, and at the same time inhibits tau’s assembly into PHFs.	SIGNOR-275442
P07949	Q16539	1	phosphorylation	up-regulates	0.332	Dually phosphorylated on thr-180 and tyr-182 by the map2ks map2k3/mkk3, map2k4/mkk4 and map2k6/mkk6 in response to inflammatory citokines, environmental stress or growth factors, which activates the enzyme.	SIGNOR-40493
P17676	O96013	0	phosphorylation	up-regulates activity	0.2	Importantly, we found that PAK4 enhanced CEBPB phosphorylation on Thr 235.\|In summary, we showed that PAK4 mediated CEBPB activation upregulated CLDN4 expression to promote breast cancer cell migration and invasion.	SIGNOR-280055

Q9Y4K4

P49841

1

phosphorylation

down-regulates

0.2

Gckr can phosphorylate an n-terminal recombinant fusion protein of gsk3_ and enhance the in vivo phosphorylation of gsk3_ on serine 9reduction of gckr expression inhibits wnt3a-induced phosphorylation of gsk3_ at serine 9 and decreases the accumulation of cytosolic _-catenin.

SIGNOR-148908

P15311

Q13464

0

phosphorylation

up-regulates

0.732

Activation of ezrin is mediated by initial pip2 binding and subsequent phosphorylation of threonine 567. We performed an in vitro kinase assay with 80 selected kinases on an ezrin peptide containing the t567 phosphorylation site (figure 3a). In this screen, we identified the mst and rock kinases as the most potent kinases for the ezrin peptide

SIGNOR-185567

P05129

P41594

1

phosphorylation

up-regulates activity

0.415

Thus, we showed that it is phosphorylation of Ser-839, not Thr-840, that is absolutely required for the unique Ca2+ oscillations produced by mGluR5 activation. The Thr-840 residue is important only in that it is permissive for the PKC-dependent phosphorylation of Ser-839.

SIGNOR-249289

Q8IXI1

O60260

0

polyubiquitination

down-regulates quantity by destabilization

0.2

PINK1 phosphorylates Miro, a component of the primary motor/adaptor complex that anchors kinesin to the mitochondrial surface. The phosphorylation of Miro activates proteasomal degradation of Miro in a Parkin-dependent manner.

SIGNOR-272726

Q9Y6D9

P53350

0

phosphorylation

up-regulates activity

0.464

These findings indicate mechanistic roles contributed by protein phosphorylation and Plk1 to the SAC activity of Mad1.Here, we have studied the phosphorylation of Mad1 and mapped using liquid chromatography-tandem mass spectrometry several phosphorylated amino acids in this protein. One phosphorylated residue, Thr680, was characterized to be important for the kinetochore localization of Mad1 and its SAC function.

SIGNOR-276173

O15111

O00141

0

phosphorylation

up-regulates activity

0.26

SGK1 directly phosphorylates IKKalpha at Thr 23 and indirectly activates IKKalpha at Ser 180.|SGK1 directly phosphorylates IKKalpha at Thr-23 and indirectly activates IKKalpha at Ser-180.

SIGNOR-278987

P01019

P08246

0

cleavage

up-regulates activity

0.275

Cathepsin G, elastase, and proteinase 3 are serine proteinases released by activated neutrophils. Cathepsin G can cleave angiotensinogen to release angiotensin II, but this activity has not been previously reported for elastase or proteinase 3. In this study we show that elastase and proteinase 3 can release angiotensin I from angiotensinogen and release angiotensin II from angiotensin I and angiotensinogen.

SIGNOR-256313

Q9BXW9

Q9NS91

0

ubiquitination

up-regulates activity

0.521

In summary, these findings suggest a model, where Rad18 promotes monoubiquitination of FANCD2, and associates with a functional complex involving Rad51, BRCA2, and FANCD2 in the repair of CPT induced stalled or collapsed forks.|In this study we focused on the role of Rad18 mediated activation of FANCD2 and its functional relationship with BRCA2 and Rad51 proteins in repair of CPT induced lesions.

SIGNOR-278712

P54764

Q14938

0

transcriptional regulation

up-regulates quantity

0.2

For example, within the NFI targetome, we identified 6 collagen genes, 13 genes encoding potassium channel or glutamate receptor subunits and a range of factors related to axon guidance (e.g. Slit1, Robo1, Epha4, Epha5, Epha8)

SIGNOR-268908

Q8IW41

P25685

1

phosphorylation

up-regulates

0.463

Phosphorylation of heat shock protein 40 (hsp40/dnajb1) by mitogen-activated protein kinase-activated protein kinase 5 (mk5/prak). Mk5 phosphorylates hsp40/dnajb1 in vivo at ser-149 or/and ser-151 and ser-171 in the c-terminal domain of hsp40/dnajb1. Mk5 modestly stimulates the atp hydrolyse activity of hsp40/hsp70 complex and enhances the repression of heat shock factor 1 driven transcription by hsp40/dnajb1.

SIGNOR-203464

P30872

Q03113

2

binding

up-regulates activity

0.25

Here we systematically quantified ligand-induced interactions between 148 GPCRs and all 11 unique G alpha subunit C-termini. For each receptor, we probed chimeric G alpha subunit activation via a transforming growth factor-alpha (TGF alpha) shedding response in HEK293 cells lacking endogenous Gq/11- and G12/13- signaling. | We defined positive coupling if any member of the subfamily scored LogRAi ≥ -1 and negative coupling if all of the members scored LogRAi < -1 (Figure 3A-B). ROC analysis gives AUC = 0.78 (Figure S4A) when considering high-confidence known coupling data and suggested a threshold of LogRAi ≥ -1.0 for defining true couplings. | The score associated to this interaction has a LogRAi ≥ -1.0.

SIGNOR-256958

P37231

P45983

0

phosphorylation

down-regulates activity

0.527

The a/b domain of human ppargamma1 was phosphorylated in vivo, and this was abolished either by mutation of serine 84 to alanine (s84a) or coexpression of a phosphoprotein phosphatase. In vitro, this domain was phosphorylated by erk2 and jnk, and this was markedly reduced in the s84a mutant. Thus, phosphorylation of a mitogen-activated protein kinase site in the a/b region of ppargamma inhibits both ligand-independent and ligand-dependent transactivation functions.

SIGNOR-46518

P68400

P27695

1

phosphorylation

up-regulates activity

0.485

Here we demonstrate that APE/Ref-1 is phosphorylated by casein kinase II (CKII). This was shown for both the recombinant APE/Ref-1 protein (Km=0.55 mM) and for APE/Ref-1 expressed in COS cells. Phosphorylation of APE/Ref-1 did not alter the repair activity of the enzyme, whereas it stimulated its redox capability towards AP-1, thus promoting DNA binding activity of AP-1.

SIGNOR-250825

P24941

Q12800

1

phosphorylation

down-regulates

0.2

In vitro, lsf is phosphorylated by cyclin e/cyclin-dependent kinase 2 (cdk2), cyclin c/cdk2, and cyclin c/cdk3, predominantly on s309. Phosphorylation by cyclin c/cyclin-dependent kinase 2 following mitogenic stimulation of murine fibroblasts inhibits transcriptional activity of lsf during g1 progression

SIGNOR-184160

P12931

Q13972

1

phosphorylation

down-regulates activity

0.47

These proximal Src kinases could potentially directly or indirectly phosphorylate Rasgrf-1 upon BCR activation and thereby further increase its GEF activity.

SIGNOR-280133

Q9P2S2

Q14118

2

binding

up-regulates activity

0.262

The DGC is potentially recruited to the postsynaptic membrane though a direct neurexin–dystroglycan interaction and an indirect interaction with NL2 via the synaptic scaffolding protein S-SCAM.

SIGNOR-265460

P25440

Q9ULU4

1

relocalization

up-regulates activity

0.287

ZMYND8 and BRD2 therefore work together to protect H4Ac domains from HDAC activity.|Further, when BRD2 was depleted, ZMYND8 accumulation was lost (Fig. 2e), indicating that either BRD2, or the underlying H4Ac, is required for ZMYND8 loading.

SIGNOR-262036

Q16539

P17275

1

phosphorylation

up-regulates

0.502

These results clearly demonstrate that phosphorylation by p38 kinase is essential for the regulation of dmp1 transcription by junb and p300. phosphorylation of junb at ser-79 was found to be essential for its interaction with p300.

SIGNOR-127545

P49841

P52945

1

phosphorylation

down-regulates quantity

0.2

We show that glucose levels modulate PDX1 protein phosphorylation at a novel C-terminal GSK3 consensus that maps to serines 268 and 272. A decrease in glucose levels triggers increased turnover of the PDX1 protein in a GSK3-dependent manner, such that PDX1 phosphomutants are refractory to the destabilizing effect of low glucose

SIGNOR-255566

Q14957

P62258

2

binding

up-regulates quantity by stabilization

0.317

Here, we demonstrate that PKB/Akt directly phosphorylates NR2C on serine 1096 (S1096). In addition, we identify 14-3-3epsilon as an NR2C interactor, whose binding is dependent on S1096 phosphorylation. These data are all consistent with a model in which NR1 and NR2C oligomerize, PKB phosphorylates S1096, and 14-3-3ε binds to phosphorylated NR2C thereby promoting NR2C-containing NMDA receptor surface expression in cerebellar granule cells.

SIGNOR-262622

P53671

Q99801

1

phosphorylation

down-regulates activity

0.2

LIMK2 also downregulates NKX3.1 mRNA levels.|While WT-NKX3.1 was efficiently phosphorylated, the S185A mutant showed no phosphorylation ( xref A), confirming that LIMK2 only phosphorylates the S185 site in NKX3.1.

SIGNOR-278951

O75385

Q8N122

1

phosphorylation

down-regulates activity

0.704

ULK1 phosphorylates RPTOR at S792, S855, and S859.|When active, ULK1 inhibits MTOR complex 1 through phosphorylation of RPTOR, which has the effect of limiting RPTOR-mediated recruitment of MTOR substrates to MTOR complex 1 [ ].

SIGNOR-278461

P06748

P49450

2

binding

up-regulates activity

0.566

Here we demonstrate that prenucleosomal CENP-A is complexed with histone H4, nucleophosmin 1, and HJURPA minority of NPM1 cofractionated with prenucleosomal CENP-A, consistent with only a small proportion of total NPM1 stably associated with CENP-A. The partial overlap of NPM1 and HJURP with each other supports their formation of distinct prenucleosomal complexes with CENP-A. it is also possible that NPM1 plays a non essential role in the assembly of CENP-A nucleosomes or the nucleophosmin paralogues NPM2 and NPM3 may compensate for the absence of NPM1.

SIGNOR-263708

P25101

P09471

2

binding

up-regulates activity

0.272

Here we systematically quantified ligand-induced interactions between 148 GPCRs and all 11 unique G alpha subunit C-termini. For each receptor, we probed chimeric G alpha subunit activation via a transforming growth factor-alpha (TGF alpha) shedding response in HEK293 cells lacking endogenous Gq/11- and G12/13- signaling. | We defined positive coupling if any member of the subfamily scored LogRAi ≥ -1 and negative coupling if all of the members scored LogRAi < -1 (Figure 3A-B). ROC analysis gives AUC = 0.78 (Figure S4A) when considering high-confidence known coupling data and suggested a threshold of LogRAi ≥ -1.0 for defining true couplings. | The score associated to this interaction has a LogRAi ≥ -1.0.

SIGNOR-257253

Q15303

O00329

2

binding

up-regulates

0.395

Pi3k is the sole binding partner to six tyrosines of erbb3 and one in erbb4.

SIGNOR-146885

Q13315

Q96T60

1

phosphorylation

up-regulates

0.462

We demonstrate that pnkp is phosphorylated by the dna-dependent protein kinase (dna-pk) and ataxia-telangiectasia mutated (atm) in vitro. The major phosphorylation site for both kinases was serine 114, with serine 126 being a minor site. Purified pnkp protein with mutation of serines 114 and 126 had decreased dna kinase and dna phosphatase activities and reduced affinity for dna in vitro.

SIGNOR-176008

Q96G74

P68400

0

phosphorylation

up-regulates activity

0.2

Here we show that phosphorylation of the human deubiquitinase DUBA (OTUD5) at a single residue, Ser177, is both necessary and sufficient to activate the enzyme. Treatment with CK2 could activate DUBA purified from E. coli, and this activity was associated with a species monophosphorylated at Ser177 (Fig. 1d).

SIGNOR-265872

P10636-2

P05771

0

phosphorylation

down-regulates activity

0.258

We have studied the relationship between the phosphorylation oftau by several kinases (MARK, PKA, MAPK, GSK3) and its assembly into PHFs. By contrast, MARK and PKA phosphorylate several sites within the repeats (notably theKXGS motifs including Ser262, Ser324, and Ser356, plus Ser320); in addition PKA phosphorylates somesites in the flanking domains, notably Ser214. This type of phosphorylation strongly reduces tau’s affinityfor microtubules, and at the same time inhibits tau’s assembly into PHFs.

SIGNOR-275442

P07949

Q16539

1

phosphorylation

up-regulates

0.332

Dually phosphorylated on thr-180 and tyr-182 by the map2ks map2k3/mkk3, map2k4/mkk4 and map2k6/mkk6 in response to inflammatory citokines, environmental stress or growth factors, which activates the enzyme.

SIGNOR-40493

P17676

O96013

0

phosphorylation

up-regulates activity

0.2

Importantly, we found that PAK4 enhanced CEBPB phosphorylation on Thr 235.|In summary, we showed that PAK4 mediated CEBPB activation upregulated CLDN4 expression to promote breast cancer cell migration and invasion.

SIGNOR-280055