General Information:

Id: 122
Diseases: Alzheimer disease - [OMIM]
Mammalia
review
Reference: Grimes CA and Jope RS(2001) The multifaceted roles of glycogen synthase kinase 3beta in cellular signaling Prog. Neurobiol. 65: 391-426 [PMID: 11527574]

Interaction Information:

Comment GSK3beta is activated by amyloid beta peptide and phosphorylates APP.
Formal Description
Interaction-ID: 419

gene/protein

GSK3B

increases_phosphorylation of

gene/protein

APP

activated by amyloid beta peptide
Drugbank entries Show/Hide entries for GSK3B or APP
Comment GSK3B phosphorylates APC.
Formal Description
Interaction-ID: 420

gene/protein

GSK3B

increases_phosphorylation of

gene/protein

APC

Drugbank entries Show/Hide entries for GSK3B
Comment IRS1 is phosphorylated by GSK3B.
Formal Description
Interaction-ID: 445

gene/protein

GSK3B

increases_phosphorylation of

gene/protein

IRS1

Drugbank entries Show/Hide entries for GSK3B or IRS1
Comment Myelin basic protein (MBP) is phosphorylated by GSK3B.
Formal Description
Interaction-ID: 446

gene/protein

GSK3B

increases_phosphorylation of

gene/protein

MBP

Drugbank entries Show/Hide entries for GSK3B
Comment MAP1B and MAP2 also are phosphorylated by GSK3beta.
Formal Description
Interaction-ID: 447

gene/protein

GSK3B

increases_phosphorylation of

gene/protein

MAP1B

Drugbank entries Show/Hide entries for GSK3B
Comment MAP1B and MAP2 also are phosphorylated by GSK3beta.
Formal Description
Interaction-ID: 450

gene/protein

GSK3B

increases_phosphorylation of

gene/protein

MAP2

Drugbank entries Show/Hide entries for GSK3B or MAP2
Comment Ninein (NN) is phosphorylated by GSK3B.
Formal Description
Interaction-ID: 452

gene/protein

GSK3B

increases_phosphorylation of

gene/protein

NIN

Drugbank entries Show/Hide entries for GSK3B
Comment GSK3beta phosphorylates TAU / MAPT, which might contribute to neurofibrillary tangle formation.
Formal Description
Interaction-ID: 453

gene/protein

GSK3B

increases_phosphorylation of

gene/protein

MAPT

Drugbank entries Show/Hide entries for GSK3B
Comment GSK3beta phosphorylated c-Jun in vitro at three sites, including Thr-239, Ser-243, and Ser-249, and decreased its DNA binding activity.
Formal Description
Interaction-ID: 454

gene/protein

GSK3B

increases_phosphorylation of

gene/protein

JUN

Drugbank entries Show/Hide entries for GSK3B or JUN
Comment Inhibition of GSK3B results in increased beta-catenin levels, its translocation to the nucleus, and facilitation of Tcf/Lef-mediated transcription.
Formal Description
Interaction-ID: 455

gene/protein

GSK3B

decreases_quantity of

gene/protein

CTNNB1

by phosphorylating beta-catenin, targeting it for degradation;
Drugbank entries Show/Hide entries for GSK3B or CTNNB1
Comment CEBPA is phosphorylated by GSK3b.
Formal Description
Interaction-ID: 456

gene/protein

GSK3B

increases_phosphorylation of

gene/protein

CEBPA

Drugbank entries Show/Hide entries for GSK3B
Comment CREB is phosphorylated by GSK3b.
Formal Description
Interaction-ID: 457

gene/protein

GSK3B

increases_phosphorylation of

gene/protein

CREB1

Drugbank entries Show/Hide entries for GSK3B or CREB1
Comment GSK3beta has an inhibitory effect on the activation of HSF-1.
Formal Description
Interaction-ID: 458

gene/protein

GSK3B

decreases_activity of

gene/protein

HSF1

Drugbank entries Show/Hide entries for GSK3B
Comment GSK3beta can phosphorylate serine residues 38, 42, and 62, and threonine residue 58 within the transactivation domain of Myc, sites considered important for regulation of Myc transcriptional activity in vivo.
Formal Description
Interaction-ID: 459

gene/protein

GSK3B

increases_phosphorylation of

gene/protein

MYC

the serine residues 38, 42, and 62, and threonine residue 58 within the transactivation domain of Myc.
Drugbank entries Show/Hide entries for GSK3B
Comment GSK3B is regulated by Wnt signaling. In the absence of Wnt, GSK3B is complexed with Axin and APC and phosphorylates beta-catenin, targeting it for degradation.
Formal Description
Interaction-ID: 463

process

canonical Wnt signaling pathway

affects_activity of

gene/protein

GSK3B

Drugbank entries Show/Hide entries for GSK3B
Comment Phosphorylation of Axin by GSK3B stabilizes Axin.
Formal Description
Interaction-ID: 464

gene/protein

GSK3B

increases_phosphorylation of

gene/protein

AXIN1

Drugbank entries Show/Hide entries for GSK3B or AXIN1
Comment GSK3B is complexed with Axin and APC and phosphorylates beta-catenin, targeting it for degradation.
Formal Description
Interaction-ID: 465

gene/protein

GSK3B

interacts (colocalizes) with

complex/PPI

APC-AXIN1-CTNNB1 complex

Drugbank entries Show/Hide entries for GSK3B
Comment GSK3B inhibited by phosphorylation at Ser9 could be reactivated with protein phosphatase 2A.
Formal Description
Interaction-ID: 479

complex/PPI

Protein phosphatase 2A

decreases_phosphorylation of

protein modification

GSK3B-phosSer9

Comment GSK3B inhibited by phosphorylation at Ser9 could be reactivated with protein phosphatase 2A.
Formal Description
Interaction-ID: 480

complex/PPI

Protein phosphatase 2A

increases_activity of

gene/protein

GSK3B

Drugbank entries Show/Hide entries for GSK3B
Comment GSK3B phosphorylates Thr-743 of the amyloid precursor protein.
Formal Description
Interaction-ID: 481

gene/protein

GSK3B

increases_phosphorylation of

gene/protein

APP

at Thr743
Drugbank entries Show/Hide entries for GSK3B or APP
Comment GSK3B increases the cellular maturation of the amyloid precursor protein which may alter the production of the Alzheimer's disease-associated amyloid-beta (Abeta) peptide.
Formal Description
Interaction-ID: 482

gene/protein

GSK3B

increases_processing of

gene/protein

APP

Drugbank entries Show/Hide entries for GSK3B or APP
Comment GSK3B increases the cellular maturation of the amyloid precursor protein which may alter the production of the Alzheimer's disease-associated amyloid-beta (Abeta) peptide.
Formal Description
Interaction-ID: 487

gene/protein

GSK3B

affects_quantity of

gene/protein

Amyloid beta peptide

Drugbank entries Show/Hide entries for GSK3B
Comment Ser-9 of GSK3beta is phosphorylated (and thus inhibited) by protein kinase A.
Formal Description
Interaction-ID: 491

gene/protein

PRKAR2A

increases_phosphorylation of

gene/protein

GSK3B

at Ser9
Drugbank entries Show/Hide entries for GSK3B
Comment ACLY is phosphorylated by GSK3beta.
Formal Description
Interaction-ID: 492

gene/protein

GSK3B

increases_phosphorylation of

gene/protein

ACLY

Drugbank entries Show/Hide entries for GSK3B
Comment GSK3beta phosphorylates PPP1R2.
Formal Description
Interaction-ID: 493

gene/protein

GSK3B

increases_phosphorylation of

gene/protein

PPP1R2

Drugbank entries Show/Hide entries for GSK3B
Comment Lithium, the primary therapeutic agent for bipolar mood disorder, is a selective inhibitor of GSK3beta.
Formal Description
Interaction-ID: 494

drug/chemical compound

Lithium

decreases_activity of

gene/protein

GSK3B

Drugbank entries Show/Hide entries for Lithium or GSK3B
Comment GSK3B phosphorylates eIF2B at Ser-540 and inhibits its activity.
Formal Description
Interaction-ID: 495

gene/protein

GSK3B

increases_phosphorylation of

gene/protein

EIF2B5

at Ser540, hereby inhibiting EIF2B5.
Drugbank entries Show/Hide entries for GSK3B
Comment GSK3B phosphorylates eIF2B at Ser-540 and inhibits its activity.
Formal Description
Interaction-ID: 496

gene/protein

GSK3B

decreases_activity of

gene/protein

EIF2B5

by phosphorylation at Ser540.
Drugbank entries Show/Hide entries for GSK3B
Comment Lithium activates the Wnt signaling pathway.
Formal Description
Interaction-ID: 570

drug/chemical compound

Lithium

increases_activity of

process

canonical Wnt signaling pathway

Drugbank entries Show/Hide entries for Lithium
Comment Lithium treatment resulted in decreased levels of Axin.
Formal Description
Interaction-ID: 583

drug/chemical compound

Lithium

decreases_quantity of

gene/protein

AXIN1

Drugbank entries Show/Hide entries for Lithium or AXIN1
Comment Lithium reduced tau phosphorylation.
Formal Description
Interaction-ID: 588

drug/chemical compound

Lithium

decreases_quantity of

protein modification

MAPT-phos

Drugbank entries Show/Hide entries for Lithium
Comment Maleimide and indirubin caused selective and potent inhibition of GSK3beta.
Formal Description
Interaction-ID: 593

drug/chemical compound

Maleimide

decreases_activity of

gene/protein

GSK3B

Drugbank entries Show/Hide entries for GSK3B
Comment Maleimide and indirubin caused selective and potent inhibition of GSK3beta.
Formal Description
Interaction-ID: 594

drug/chemical compound

Indirubin

decreases_activity of

gene/protein

GSK3B

Drugbank entries Show/Hide entries for GSK3B
Comment Increased nuclear GSK3beta was induced by heat shock.
Formal Description
Interaction-ID: 618

process

response to heat

increases_quantity of

gene/protein

GSK3B

in nucleus
Drugbank entries Show/Hide entries for GSK3B
Comment Cell stressors can modulate the activity of GSK3beta, as both heat shock and oxidative stress can cause inhibition of GSK3beta.
Formal Description
Interaction-ID: 620

process

response to oxidative stress

decreases_activity of

gene/protein

GSK3B

Drugbank entries Show/Hide entries for GSK3B
Comment Protein kinase C alpha phosphorylates and inactivates GSK3B.
Formal Description
Interaction-ID: 646

gene/protein

PRKCA

increases_phosphorylation of

gene/protein

GSK3B

Drugbank entries Show/Hide entries for PRKCA or GSK3B
Comment Protein kinase C alpha phosphorylates and inactivates GSK3B.
Formal Description
Interaction-ID: 647

gene/protein

PRKCA

decreases_activity of

gene/protein

GSK3B

Drugbank entries Show/Hide entries for PRKCA or GSK3B
Comment Protein kinase C beta phosphorylates and inactivates GSK3B.
Formal Description
Interaction-ID: 648

gene/protein

PRKCB

increases_phosphorylation of

gene/protein

GSK3B

hereby inactivating GSK3B.
Drugbank entries Show/Hide entries for PRKCB or GSK3B
Comment Protein kinase C beta phosphorylates and inactivates GSK3B.
Formal Description
Interaction-ID: 649

gene/protein

PRKCB

decreases_activity of

gene/protein

GSK3B

Drugbank entries Show/Hide entries for PRKCB or GSK3B
Comment Protein kinase C gamma phosphorylates and inactivates GSK3B.
Formal Description
Interaction-ID: 650

gene/protein

PRKCG

increases_phosphorylation of

gene/protein

GSK3B

Drugbank entries Show/Hide entries for GSK3B
Comment Protein kinase C gamma phosphorylates and inactivates GSK3B.
Formal Description
Interaction-ID: 651

gene/protein

PRKCG

decreases_activity of

gene/protein

GSK3B

Drugbank entries Show/Hide entries for GSK3B
Comment Protein kinase C (gamma but not epsilon) phosphorylates and inactivates GSK3B.
Formal Description
Interaction-ID: 652

gene/protein

PRKCE

NOT affects_phosphorylation of

gene/protein

GSK3B

Drugbank entries Show/Hide entries for GSK3B
Comment Protein kinase C (gamma but not epsilon) phosphorylates and inactivates GSK3B.
Formal Description
Interaction-ID: 653

gene/protein

PRKCE

NOT decreases_activity of

gene/protein

GSK3B

Drugbank entries Show/Hide entries for GSK3B
Comment Active AKT (phosphorylated at Ser-473 and Thr-308) reduces activity of GSK3B by phosphorylation of Ser-9.
Formal Description
Interaction-ID: 671

protein modification

AKT1-phosSer473Thr308

increases_phosphorylation of

gene/protein

GSK3B

at Ser-9, hereby reducing the activity of GSK3B.
Drugbank entries Show/Hide entries for GSK3B
Comment Active AKT (phosphorylated at Ser-473 and Thr-308) reduces activity of GSK3B by phosphorylation of Ser-9.
Formal Description
Interaction-ID: 672

protein modification

AKT1-phosSer473Thr308

decreases_activity of

gene/protein

GSK3B

by phosphorylation of GSK3B at Ser9
Drugbank entries Show/Hide entries for GSK3B
Comment Insulin-like growth factor-1 (IGF-1) inhibits GSK3B through increased Ser-9 phosphorylation in a PI3K-dependent manner.
Formal Description
Interaction-ID: 678

gene/protein

IGF1

decreases_activity of

gene/protein

GSK3B

by increased Ser9 phosphorylation
Drugbank entries Show/Hide entries for IGF1 or GSK3B
Comment Endothelin-1 inhibites GSK3B through Ser-9 phosphorylation in a PI3K-dependent manner in myocytes.
Formal Description
Interaction-ID: 679

gene/protein

EDN1

decreases_activity of

gene/protein

GSK3B

in myocytes; by phosphorylation of GSK3B at Ser9
Drugbank entries Show/Hide entries for GSK3B
Comment Endothelin-1 inhibites GSK3B through Ser-9 phosphorylation in a PI3K-dependent manner in myocytes.
Formal Description
Interaction-ID: 680

gene/protein

EDN1

increases_phosphorylation of

gene/protein

GSK3B

at Ser9, hereby inhibiting GSK3B.
Drugbank entries Show/Hide entries for GSK3B
Comment GBP binding inhibited GSK3B-mediated phosphorylation of the intact tau protein, possibly due to steric hindrance.
Formal Description
Interaction-ID: 685

gene/protein

GBP

decreases_phosphorylation of

gene/protein

MAPT

GBP binding inhibited GSK3B-mediated phosphorylation of the intact tau protein.
Comment Complex formation between GSK3B and proteins in the GBP family is an important mechanism for the inhibitory control of GSK3B activity.
Formal Description
Interaction-ID: 686

gene/protein

GBP

interacts (colocalizes) with

gene/protein

GSK3B

This is an important mechanism for the inhibitory control of GSK3B activity.
Drugbank entries Show/Hide entries for GSK3B
Comment Opposite to the inhibitory effect of complex formation with GBP, GSK3B activity is enhanced by binding to Axin, which is both a substrate for phosphorylation by GSK3B and enhances GSK3B-induced phosphorylation of beta-catenin.
Formal Description
Interaction-ID: 687

gene/protein

AXIN1

increases_activity of

gene/protein

GSK3B

Drugbank entries Show/Hide entries for AXIN1 or GSK3B
Comment In the absence of Wnt, GSK3B is complexed with Axin and APC and phosphorylates beta-catenin, targeting it for degradation.
Formal Description
Interaction-ID: 754

gene/protein

GSK3B

increases_phosphorylation of

gene/protein

CTNNB1

in the absence of Wnt and if GSK3B is complexed with Axin and APC;
Drugbank entries Show/Hide entries for GSK3B or CTNNB1
Comment Frat1 binds and inactivates GSK3B, blocking phosphorylation of beta-catenin.
Formal Description
Interaction-ID: 760

gene/protein

FRAT1

interacts (colocalizes) with

gene/protein

GSK3B

Drugbank entries Show/Hide entries for GSK3B
Comment Frat1 binds and inactivates GSK3B, blocking phosphorylation of beta-catenin.
Formal Description
Interaction-ID: 761

gene/protein

FRAT1

decreases_activity of

gene/protein

GSK3B

Drugbank entries Show/Hide entries for GSK3B
Comment GSK3B phosphorylates, deactivates, and induces nuclear export of NFATc, providing a mechanism by which calcium-calcineurin signaling and GSK3B could counteract each other to regulate NFATc activity.
Formal Description
Interaction-ID: 805

gene/protein

GSK3B

increases_phosphorylation of

gene/protein

NFATC1

Drugbank entries Show/Hide entries for GSK3B
Comment NFAT induces IL-2 production.
Formal Description
Interaction-ID: 807

gene/protein

NFATC1

increases_quantity of

gene/protein

IL2

Drugbank entries Show/Hide entries for IL2
Comment Abeta-induced neurotoxicity was reduced by antisense GSK3B oligonucleotides and by the GSK3B inhibitor lithium.
Formal Description
Interaction-ID: 864

drug/chemical compound

Lithium

affects_activity of

gene/protein

Amyloid beta peptide

Drugbank entries Show/Hide entries for Lithium
Comment Abeta-activated GSK3B phosphorylated and inactivated pyruvate dehydrogenase, resulting in reduced synthesis of acetylcholine due to depletion of its precursor acetyl coenzyme A.
Formal Description
Interaction-ID: 865

gene/protein

GSK3B

increases_phosphorylation of

complex/PPI

Pyruvate dehydrogenase complex

Drugbank entries Show/Hide entries for GSK3B
Comment Mutations in the presenilin 1 gene cause an autosomal dominant inheritance of early onset Alzheimer's disease with 100% penetrance in causing Alzheimer's disease.
Formal Description
Interaction-ID: 868

gene/protein mutant

PSEN1-mut

increases_activity of

disease

Alzheimer disease

Comment Presenilin 1 can facilitate the co-localization of GSK3B and tau.
Formal Description
Interaction-ID: 907

gene/protein

PSEN1

increases_activity of

process

protein localization

of GSK3B and MAPT/TAU
Comment Presenilin 1 binds to GSK3B. Mutant forms of presenilin 1 can modify the activity and function of GSK3B.
Formal Description
Interaction-ID: 908

gene/protein

PSEN1

interacts (colocalizes) with

gene/protein

GSK3B

Drugbank entries Show/Hide entries for GSK3B
Comment Presenilin 1 is capable of modulating its activity by regulating Akt.
Formal Description
Interaction-ID: 909

gene/protein

PSEN1

affects_activity of

gene/protein

AKT1

Drugbank entries Show/Hide entries for AKT1
Comment GSK3B facilitates apoptosis.
Formal Description
Interaction-ID: 911

gene/protein

GSK3B

increases_activity of

process

apoptotic process

Drugbank entries Show/Hide entries for GSK3B
Comment GSK3 activity inhibits CREB.
Formal Description
Interaction-ID: 919

gene/protein

GSK3B

decreases_activity of

gene/protein

CREB1

Drugbank entries Show/Hide entries for GSK3B or CREB1
Comment GSK3beta phosphorylates PDH, which decreases acetylcholine synthesis.
Formal Description
Interaction-ID: 12873

gene/protein

GSK3B

increases_phosphorylation of

gene/protein

PDP1

Drugbank entries Show/Hide entries for GSK3B
Comment GSK3beta phosphorylates PDH, which decreases acetylcholine synthesis.
Formal Description
Interaction-ID: 12874

gene/protein

PDP1

decreases_activity of

process

acetylcholine biosynthetic process

if PDH is phosphorylated
Comment GSK3beta is complexed with Axin and APC.
Formal Description
Interaction-ID: 12875

gene/protein

GSK3B

interacts (colocalizes) with

gene/protein

APC

Drugbank entries Show/Hide entries for GSK3B
Comment GSK3beta is complexed with Axin and APC.
Formal Description
Interaction-ID: 12876

gene/protein

GSK3B

interacts (colocalizes) with

gene/protein

AXIN1

Drugbank entries Show/Hide entries for GSK3B or AXIN1
Comment GSK3beta can phosphorylate serine residues 38, 42, and 62, and threonine residue 58 within the transactivation domain of Myc, sites considered important for regulation of Myc transcriptional activity in vivo.
Formal Description
Interaction-ID: 12923

gene/protein

GSK3B

affects_activity of

gene/protein

MYC

via phosphorylation
Drugbank entries Show/Hide entries for GSK3B
Comment Ser-9 of GSK3beta is phosphorylated (and thus inhibited) by protein kinase A.
Formal Description
Interaction-ID: 12925

gene/protein

PRKAR2A

decreases_activity of

gene/protein

GSK3B

if GSK3B is phosphorylated at Ser9.
Drugbank entries Show/Hide entries for GSK3B
Comment H2O2 reduces the activity of GSK3beta.
Formal Description
Interaction-ID: 12927

drug/chemical compound

H2O2

decreases_activity of

gene/protein

GSK3B

Drugbank entries Show/Hide entries for GSK3B
Comment Cell stressors can modulate the activity of GSK3beta, as both heat shock and oxidative stress can cause inhibition of GSK3beta.
Formal Description
Interaction-ID: 12929

process

response to heat

decreases_activity of

gene/protein

GSK3B

Drugbank entries Show/Hide entries for GSK3B
Comment Insulin-like growth factor-1 (IGF-1) inhibits GSK3B through increased Ser-9 phosphorylation in a PI3K-dependent manner.
Formal Description
Interaction-ID: 12930

gene/protein

IGF1

increases_phosphorylation of

gene/protein

GSK3B

at Ser9
Drugbank entries Show/Hide entries for IGF1 or GSK3B
Comment GSK3B phosphorylates, deactivates, and induces nuclear export of NFATc, providing a mechanism by which calcium-calcineurin signaling and GSK3B could counteract each other to regulate NFATc activity.
Formal Description
Interaction-ID: 12947

gene/protein

GSK3B

decreases_activity of

gene/protein

NFATC1

Drugbank entries Show/Hide entries for GSK3B
Comment GSK3B phosphorylates, deactivates, and induces nuclear export of NFATc, providing a mechanism by which calcium-calcineurin signaling and GSK3B could counteract each other to regulate NFATc activity.
Formal Description
Interaction-ID: 12948

gene/protein

GSK3B

increases_transport of

gene/protein

NFATC1

GSK3B phosphorylates, deactivates, and induces nuclear export of NFATc.
Drugbank entries Show/Hide entries for GSK3B
Comment Abeta-activated GSK3B phosphorylated and inactivated pyruvate dehydrogenase, resulting in reduced synthesis of acetylcholine due to depletion of its precursor acetyl coenzyme A.
Formal Description
Interaction-ID: 12957

gene/protein

GSK3B

affects_quantity of

drug/chemical compound

Acetylcholine

Drugbank entries Show/Hide entries for GSK3B or Acetylcholine
Comment GSK3beta is activated by amyloid beta peptide and phosphorylates APP.
Formal Description
Interaction-ID: 14051

gene/protein

Amyloid beta peptide

increases_activity of

gene/protein

GSK3B

Drugbank entries Show/Hide entries for GSK3B
Comment Insulin-like growth factor-1 (IGF-1) inhibits GSK3B through increased Ser-9 phosphorylation in a PI3K-dependent manner.
Formal Description
Interaction-ID: 50125

gene/protein

IGF1

increases_phosphorylation of

gene/protein

GSK3B

at Ser9
Drugbank entries Show/Hide entries for IGF1 or GSK3B
Comment Lithium reduced tau phosphorylation.
Formal Description
Interaction-ID: 64421

drug/chemical compound

Lithium

decreases_phosphorylation of

gene/protein

MAPT

Drugbank entries Show/Hide entries for Lithium
Comment Abeta-activated GSK3B phosphorylated and inactivated pyruvate dehydrogenase, resulting in reduced synthesis of acetylcholine due to depletion of its precursor acetyl coenzyme A.
Formal Description
Interaction-ID: 72065

gene/protein

GSK3B

decreases_activity of

complex/PPI

Pyruvate dehydrogenase complex

via phosphorylation
Drugbank entries Show/Hide entries for GSK3B
Comment GSK3beta phosphorylates PDH, which decreases acetylcholine synthesis.
Formal Description
Interaction-ID: 133776

gene/protein

GSK3B

increases_quantity of

protein modification

PDP1-phos

Drugbank entries Show/Hide entries for GSK3B
Comment CREB is phosphorylated by GSK3b.
Formal Description
Interaction-ID: 153728

gene/protein

GSK3B

increases_quantity of

protein modification

CREB1-phos

Drugbank entries Show/Hide entries for GSK3B
Comment CREB is phosphorylated by GSK3b.
Formal Description
Interaction-ID: 153729

gene/protein

GSK3B

increases_activity of

phenotype

increased CREB1-phos level

Drugbank entries Show/Hide entries for GSK3B