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p(HGNC:CDK5)

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Entity

Name
CDK5
Namespace
HGNC
Namespace Version
20180215
Namespace URL
https://arty.scai.fraunhofer.de/artifactory/bel/namespace/hgnc/hgnc-20180215.belns

Appears in Networks 15

APP processing in Alzheimer's disease v1.0.1

APP processing in Alzheimer's disease

Proteolytic processing of Alzeimer's beta-amyloid precursor protein v1.0.1

Abnormal Alzheimer-like phosphorylation of tau-protein by cyclin-dependent kinases cdk2 and cdk5 v1.0.0

Molecular chaperones and regulation of tau quality control: strategies for drug discovery in tauopathies v1.0.0

TAU and Interaction Partners v1.2.5

TAU Interactions Section of NESTOR

Tau Modifications v1.9.5

Tau Modifications Sections of NESTOR

Inflammasome Involvement in Alzheimer’s Disease v1.0.0

Amyloid-Binding Alcohol Dehydrogenase (ABAD) Inhibitors for the Treatment of Alzheimer’s Disease v1.0.0

Protein phosphatase 2A dysfunction in Alzheimer’s disease v1.0.0

Axonal Transport, Tau Protein, and Neurodegeneration in Alzheimer’s Disease v1.0.0

PP2A and Alzheimer Disease v1.0.0

Alzheimer’s disease and the autophagic-lysosomal system v1.0.0

Caenorhabditis elegans models of tauopathy v1.0.0

Nuclear Factor Kappa-light-chain-enhancer of Activated B Cells (NF-κB) - a Friend, a Foe, or a Bystander - in the Neurodegenerative Cascade and Pathogenesis of Alzheimer's Disease v1.0.0

mTOR-Related Brain Dysfunctions in Neuropsychiatric Disorders v1.0.0

In-Edges 43

a(HBP:HBP00067) decreases act(p(HGNC:CDK5)) View Subject | View Object

We and others have also found that sAPPalpha can inhibit stress-induced CDK5 activation and participate in various neuroprotective reagent-mediated excitoprotection [44,59-61] PubMed:21214928

Appears in Networks:
Annotations
Confidence
High
MeSH
Neurons

complex(a(GO:"protein phosphatase type 2A complex"), p(HGNC:CDK5)) hasComponent p(HGNC:CDK5) View Subject | View Object

Appears in Networks:

a(GO:microtubule) association p(HGNC:CDK5) View Subject | View Object

Fig. 5 shows that the 31 kDa kinase is included in the MAP fraction after three or more cycles of microtubule assembly (lanes l-6), and is also associated with PHFs (lane 7) PubMed:8282104

Appears in Networks:
Annotations
Confidence
High

a(HBP:HBP00006) association p(HGNC:CDK5) View Subject | View Object

Fig. 5 shows that the 31 kDa kinase is included in the MAP fraction after three or more cycles of microtubule assembly (lanes l-6), and is also associated with PHFs (lane 7) PubMed:8282104

Appears in Networks:
Annotations
Confidence
High

complex(a(HBP:HBP00172), p(HGNC:CDK5)) hasComponent p(HGNC:CDK5) View Subject | View Object

Appears in Networks:

path(MESH:"Alzheimer Disease") positiveCorrelation p(HGNC:CDK5) View Subject | View Object

Thus, we now know three kinases, cdk5, MAP kinase, and GSK-3, all of which are present in neurons, which are capable of transforming tau into the Alzheimer-like state, and therefore could account for the pathological phosphorylation of tau in Alzheimer brains PubMed:8282104

Appears in Networks:
Annotations
Confidence
High
MeSH
Neurons

p(HGNC:CDC37) positiveCorrelation act(p(HGNC:CDK5)) View Subject | View Object

Western blot analysis for a panel of tau kinases showed that only the levels of endogenous Cdk5 and Akt were significantly reduced by Cdc37 siRNA; the levels of GSK3-Beta and Mark2 (microtubule affinity regulating kinase 2) were largely unchanged PubMed:21367866

Appears in Networks:

a(CHEBI:staurosporine) decreases act(p(HGNC:CDK5)) View Subject | View Object

The kinase activity was inhibited by staurosporine, isopentanyladenine and olomoucine in a dose dependent manner. Kinetic studies indicated Ki values of 39 nM, 38 microM and 8 microM, respectively for staurosporine, isopentanyladenine and olomoucine. PubMed:8726973

Appears in Networks:

a(HBP:isopentanyladenine) decreases act(p(HGNC:CDK5)) View Subject | View Object

The kinase activity was inhibited by staurosporine, isopentanyladenine and olomoucine in a dose dependent manner. Kinetic studies indicated Ki values of 39 nM, 38 microM and 8 microM, respectively for staurosporine, isopentanyladenine and olomoucine. PubMed:8726973

Appears in Networks:

a(HBP:olomoucine) decreases act(p(HGNC:CDK5)) View Subject | View Object

The kinase activity was inhibited by staurosporine, isopentanyladenine and olomoucine in a dose dependent manner. Kinetic studies indicated Ki values of 39 nM, 38 microM and 8 microM, respectively for staurosporine, isopentanyladenine and olomoucine. PubMed:8726973

Appears in Networks:

complex(p(HGNC:CDK5), p(HGNC:CDK5R1)) hasComponent p(HGNC:CDK5) View Subject | View Object

Appears in Networks:

complex(p(HGNC:CDK5), p(HGNC:CDK5R1)) increases act(p(HGNC:CDK5)) View Subject | View Object

To perform its function, Cdk5 must bind to the neuron-specific regulatory subunit protein p35, which is beneficial for neuronal development (Tsai et al. 1994; Chae et al. 1997). However, truncation of p35 and conversion to p25 (Patrick et al. 1999) is found in the forebrain of rats after focal cerebral ischemia and in AD patients, and these alterations are deleterious to the brain PubMed:26118667

Appears in Networks:

p(HGNC:CDK5R1) increases act(p(HGNC:CDK5)) View Subject | View Object

TTBK1-Tg mice show significant age-dependent memory impairment as determined by radial arm water maze test, which is associated with enhancement of tau and neurofilament phosphorylation, increased levels of p25 and p35, both activators of cyclin-dependent protein kinase 5 (CDK5), enhanced calpain I activity, and reduced levels of hippocampal NMDA receptor types 2B (NR2B) and D. Enhanced CDK5/p35 complex formation is strongly correlated with dissociation of F-actin from p35, suggesting the inhibitory mechanism of CDK5/p35 complex formation by F-actin. PubMed:21548880

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complex(p(HGNC:CDK5), p(HGNC:MAPT, pmod(Ph, Ser, 202))) hasComponent p(HGNC:CDK5) View Subject | View Object

Appears in Networks:

complex(p(HGNC:CDK5), p(HGNC:MAPT, pmod(Ph, Ser, 396))) hasComponent p(HGNC:CDK5) View Subject | View Object

Appears in Networks:

complex(p(HGNC:CDK5), p(HGNC:MAPT, pmod(Ph, Ser, 404))) hasComponent p(HGNC:CDK5) View Subject | View Object

Appears in Networks:

complex(p(HGNC:CDK5), p(HGNC:MAPT, pmod(Ph, Thr, 212))) hasComponent p(HGNC:CDK5) View Subject | View Object

Appears in Networks:

complex(p(HGNC:CDK5), p(HGNC:MAPT, pmod(Ph, Thr, 217))) hasComponent p(HGNC:CDK5) View Subject | View Object

Appears in Networks:

m(MIRBASE:"hsa-mir-125b-1") increases act(p(HGNC:CDK5), ma(kin)) View Subject | View Object

In primary neurons, overexpression of miR-125b causes tau hyperphosphorylation and an upregulation of p35, cdk5, and p44/42-MAPK signaling. In parallel, the phosphatases DUSP6 and PPP1CA and the anti-apoptotic factor Bcl-W are downregulated as direct targets of miR-125b. Knockdown of these phosphatases induces tau hyperphosphorylation, and overexpression of PPP1CA and Bcl-W prevents miR-125b-induced tau phosphorylation, suggesting that they mediate the effects of miR-125b on tau. Conversely, suppression of miR-125b in neurons by tough decoys reduces tau phosphorylation and kinase expression/activity. Injecting miR-125b into the hippocampus of mice impairs associative learning and is accompanied by downregulation of Bcl-W, DUSP6, and PPP1CA, resulting in increased tau phosphorylation in vivo. Importantly, DUSP6 and PPP1CA are also reduced in AD brains. PubMed:25001178

Appears in Networks:

act(p(HGNC:MAPK1), ma(kin)) positiveCorrelation act(p(HGNC:CDK5), ma(kin)) View Subject | View Object

Since Erk1/2 activity has been shown to induce cdk5 (Harada et al, 2001), miR-125b-induced Erk1/2 activation through DUSP6 downregulation might ultimately stimulate aberrant cdk5/p35 activation and, consequently, enhance pathological tau phosphorylation at multiple sites PubMed:25001178

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p(HGNC:TTBK1) increases act(p(HGNC:CDK5)) View Subject | View Object

Activates cdk5 and GSK3; genetic variation protects against AD in Spanish cohort PubMed:20096481

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p(HGNC:IL18) increases p(HGNC:CDK5) View Subject | View Object

Pro-inflammatory IL-18 increases AD-associated A beta deposition in human neuron-like cells in culture [55]. IL-18 also increases the expression of glycogen synthase kinase 3 beta (GSK-3 beta ) and cyclin-dependent kinase 5, both of which are involved in hyperphos- phorylation of the tau protein [56]. PubMed:27314526

Appears in Networks:
Annotations
Confidence
High
MeSH
Alzheimer Disease
NeuroMMSigDB
Amyloidogenic subgraph
NeuroMMSigDB
Cyclin-CDK subgraph
NeuroMMSigDB
GSK3 subgraph
NeuroMMSigDB
Interleukin signaling subgraph
NeuroMMSigDB
Tau protein subgraph

path(MESH:"Alzheimer Disease") positiveCorrelation p(HGNC:CDK5) View Subject | View Object

Inactivation of Prdx-2 is controlled by a kinase that has been shown to be elevated in AD, CDK5, 107, 108 which phosphorylates Thr 89 and results in deactivation of Prdx-2. PubMed:30444369

Appears in Networks:
Annotations
MeSH
Neurons

a(GO:"microtubule cytoskeleton") negativeCorrelation act(p(HGNC:CDK5)) View Subject | View Object

Apart from affecting tau phosphorylation, abnormal activation of GSK3β, cdk5, and ERK has been linked to cytoskeletal abnormalities (microtubules, neurofilaments), alterations in amyloid precursor protein (APP) phosphorylation and processing, impairment of neurogenesis, alterations in synaptic plasticity and induction of apoptotic processes (Reviewed in Crews and Masliah, 2010; Medina and Avila, 2013, 2014). PubMed:24653673

Appears in Networks:

a(GO:"neurofilament cytoskeleton") negativeCorrelation act(p(HGNC:CDK5)) View Subject | View Object

Apart from affecting tau phosphorylation, abnormal activation of GSK3β, cdk5, and ERK has been linked to cytoskeletal abnormalities (microtubules, neurofilaments), alterations in amyloid precursor protein (APP) phosphorylation and processing, impairment of neurogenesis, alterations in synaptic plasticity and induction of apoptotic processes (Reviewed in Crews and Masliah, 2010; Medina and Avila, 2013, 2014). PubMed:24653673

Appears in Networks:

bp(GO:"apoptotic process") positiveCorrelation act(p(HGNC:CDK5)) View Subject | View Object

Apart from affecting tau phosphorylation, abnormal activation of GSK3β, cdk5, and ERK has been linked to cytoskeletal abnormalities (microtubules, neurofilaments), alterations in amyloid precursor protein (APP) phosphorylation and processing, impairment of neurogenesis, alterations in synaptic plasticity and induction of apoptotic processes (Reviewed in Crews and Masliah, 2010; Medina and Avila, 2013, 2014). PubMed:24653673

Appears in Networks:

bp(GO:"negative regulation of synaptic plasticity") positiveCorrelation act(p(HGNC:CDK5)) View Subject | View Object

Apart from affecting tau phosphorylation, abnormal activation of GSK3β, cdk5, and ERK has been linked to cytoskeletal abnormalities (microtubules, neurofilaments), alterations in amyloid precursor protein (APP) phosphorylation and processing, impairment of neurogenesis, alterations in synaptic plasticity and induction of apoptotic processes (Reviewed in Crews and Masliah, 2010; Medina and Avila, 2013, 2014). PubMed:24653673

Appears in Networks:

bp(GO:neurogenesis) negativeCorrelation act(p(HGNC:CDK5)) View Subject | View Object

Apart from affecting tau phosphorylation, abnormal activation of GSK3β, cdk5, and ERK has been linked to cytoskeletal abnormalities (microtubules, neurofilaments), alterations in amyloid precursor protein (APP) phosphorylation and processing, impairment of neurogenesis, alterations in synaptic plasticity and induction of apoptotic processes (Reviewed in Crews and Masliah, 2010; Medina and Avila, 2013, 2014). PubMed:24653673

Appears in Networks:

bp(HBP:"APP processing") negativeCorrelation act(p(HGNC:CDK5)) View Subject | View Object

Apart from affecting tau phosphorylation, abnormal activation of GSK3β, cdk5, and ERK has been linked to cytoskeletal abnormalities (microtubules, neurofilaments), alterations in amyloid precursor protein (APP) phosphorylation and processing, impairment of neurogenesis, alterations in synaptic plasticity and induction of apoptotic processes (Reviewed in Crews and Masliah, 2010; Medina and Avila, 2013, 2014). PubMed:24653673

Appears in Networks:

act(complex(GO:"protein phosphatase type 2A complex")) increases act(p(HGNC:CDK5)) View Subject | View Object

Specific PP2A inhibition has been proven to lead to in vivo deregulation of many major brain Ser/Thr kinases implicated in AD, including GSK3β (Wang et al., 2010; Louis et al., 2011), cdk5 (Louis et al., 2011; Kimura et al., 2013), extracellular signal- regulated kinase (ERK) and JNK (Kins et al., 2003). PubMed:24653673

Appears in Networks:

p(HGNC:APP, pmod(Ph)) negativeCorrelation act(p(HGNC:CDK5)) View Subject | View Object

Apart from affecting tau phosphorylation, abnormal activation of GSK3β, cdk5, and ERK has been linked to cytoskeletal abnormalities (microtubules, neurofilaments), alterations in amyloid precursor protein (APP) phosphorylation and processing, impairment of neurogenesis, alterations in synaptic plasticity and induction of apoptotic processes (Reviewed in Crews and Masliah, 2010; Medina and Avila, 2013, 2014). PubMed:24653673

Appears in Networks:

path(MESH:"Alzheimer Disease") association p(HGNC:CDK5) View Subject | View Object

PP2A enzymes can also associate with protein kinases that have been linked to AD, such as glycogen synthase kinase 3β (GSK3β) and cyclin-dependent kinase 5 (cdk5; Plattner et al.,2006), and neuronal receptors, e.g., the NMDA receptor (Chan and Sucher, 2001) and the metabotropic glutamate receptor 5 (Mao et al., 2005; Arif et al., 2014). PubMed:24653673

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act(p(FPLX:PPP2)) decreases act(p(HGNC:CDK5)) View Subject | View Object

Moreover, some tau kinases as cyclin- dependent kinase 5 (cdk5) and TPKI (thiamine pyrophos- phokinase 1)/GSK3 (glycogen synthase kinase 3) are acti- vated following PP2A inhibition in starved mice [51]. PubMed:22299660

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composite(p(HBP:"Tau isoform D (383 aa)", var("p.Pro301Leu")), p(HGNC:CDK5)) hasComponent p(HGNC:CDK5) View Subject | View Object

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a(CHEBI:amphetamine) increases p(HGNC:CDK5) View Subject | View Object

Both administration of amphetamines and stimulation of D1R induce a significant increase of CDK5 gene expression and protein levels, which, at molecular level, associates with increased dendritic spine density and hyper-phosphorylation of the cytoskeletal tau protein PubMed:30061532

Appears in Networks:

a(GO:"dendritic spine") positiveCorrelation p(HGNC:CDK5) View Subject | View Object

Both administration of amphetamines and stimulation of D1R induce a significant increase of CDK5 gene expression and protein levels, which, at molecular level, associates with increased dendritic spine density and hyper-phosphorylation of the cytoskeletal tau protein PubMed:30061532

Appears in Networks:

p(HGNC:CDK5R1) negativeCorrelation act(p(HGNC:CDK5)) View Subject | View Object

Remarkably, the marked reduction of p35 levels in schizophrenic brains, which mirrors enhanced CDK5 activity [247], suggests a role for CDK5-CRMP2-dependent alterations of cytoskeleton architecture and psychiatric behavior PubMed:30061532

Appears in Networks:
Annotations
MeSH
Brain

complex(p(HGNC:CDK5), p(HGNC:DPYSL2)) hasComponent p(HGNC:CDK5) View Subject | View Object

Appears in Networks:

p(HGNC:CDK5R1, frag("?")) increases act(p(HGNC:CDK5)) View Subject | View Object

In detail, the activation of CDK5 by D1R occurs via proteolysis of p35, the binding partner of CDK5 PubMed:30061532

Appears in Networks:

act(p(HGNC:DRD1)) increases p(HGNC:CDK5) View Subject | View Object

Both administration of amphetamines and stimulation of D1R induce a significant increase of CDK5 gene expression and protein levels, which, at molecular level, associates with increased dendritic spine density and hyper-phosphorylation of the cytoskeletal tau protein PubMed:30061532

Appears in Networks:

p(HGNC:DRD1) increases p(HGNC:CDK5) View Subject | View Object

In detail, the activation of CDK5 by D1R occurs via proteolysis of p35, the binding partner of CDK5 PubMed:30061532

Appears in Networks:

p(HGNC:MAPT, pmod(HBP:hyperphosphorylation)) positiveCorrelation p(HGNC:CDK5) View Subject | View Object

Both administration of amphetamines and stimulation of D1R induce a significant increase of CDK5 gene expression and protein levels, which, at molecular level, associates with increased dendritic spine density and hyper-phosphorylation of the cytoskeletal tau protein PubMed:30061532

Appears in Networks:

path(MESH:Schizophrenia) positiveCorrelation act(p(HGNC:CDK5)) View Subject | View Object

Remarkably, the marked reduction of p35 levels in schizophrenic brains, which mirrors enhanced CDK5 activity [247], suggests a role for CDK5-CRMP2-dependent alterations of cytoskeleton architecture and psychiatric behavior PubMed:30061532

Appears in Networks:
Annotations
MeSH
Brain

Out-Edges 52

p(HGNC:CDK5) increases p(HBP:HBP00071, pmod(Ph, Thr, 654)) View Subject | View Object

AICD also contains three phosphorylation sites, including two threonine residues at 654 and 668 and a serine residue at 665. AICD has been found to be phosphorylated by PKC, calcium-calmodulin dependent-kinase II, GSK3-b, Cdk5 and c-Jun N-terminal kinase (JNK) at the Ser/Thr sites mentioned above PubMed:22122372

Appears in Networks:
Annotations
Confidence
High
MeSH
Neurons

p(HGNC:CDK5) increases p(HBP:HBP00071, pmod(Ph, Thr, 668)) View Subject | View Object

AICD also contains three phosphorylation sites, including two threonine residues at 654 and 668 and a serine residue at 665. AICD has been found to be phosphorylated by PKC, calcium-calmodulin dependent-kinase II, GSK3-b, Cdk5 and c-Jun N-terminal kinase (JNK) at the Ser/Thr sites mentioned above PubMed:22122372

Appears in Networks:
Annotations
Confidence
High
MeSH
Neurons

p(HGNC:CDK5) increases p(HBP:HBP00071, pmod(Ph, Ser, 665)) View Subject | View Object

AICD also contains three phosphorylation sites, including two threonine residues at 654 and 668 and a serine residue at 665. AICD has been found to be phosphorylated by PKC, calcium-calmodulin dependent-kinase II, GSK3-b, Cdk5 and c-Jun N-terminal kinase (JNK) at the Ser/Thr sites mentioned above PubMed:22122372

Appears in Networks:
Annotations
Confidence
High
MeSH
Neurons

p(HGNC:CDK5) directlyIncreases p(HBP:HBP00053, pmod(Ph)) View Subject | View Object

These fractions (7-9) contained several protein bands, including two with Mr = 25 and 31 kDa (Fig. 3D, lanes 3-5) and were capable of phosphorylating htau40, incorporating 3.2, 4.2 and 2.9 mol Pi per mol htau40, respectively, and inducing an A4, shift of htau40 in SDS-PAGE PubMed:8282104

Appears in Networks:
Annotations
Confidence
High

p(HGNC:CDK5) directlyIncreases p(HGNC:MAPT, pmod(Ph)) View Subject | View Object

In conclusion, this cdc2-like kinase activity towards tau occurs in brain tissue and has an Mr of 31 kDa. These features are suggestive of other cdc2-like kinases cloned recently from brain, termed nclk [ 141, PSSARLE [28], or cdk5 [42,49]. Indeed, the 31 kDa protein reacted with an antibody specific for cdk5. Thus, the kinase isolated here is very similar if not identical to cdk5. PubMed:8282104

Appears in Networks:
Annotations
Confidence
High
MeSH
Brain

p(HGNC:CDK5) directlyIncreases p(HGNC:MAPT, pmod(Ph, Ser, 199)) View Subject | View Object

The reaction with the diagnostic antibodies (Fig. 4) is similar to the examples shown previously for cdk2 (Fig. 2), MAP kinase [8], or GSK-3 [26], indicating the phosphorylation of the SP motifs for which these antibodies are sensitive (serines 199, 202, 235, 396, 404; see Fig. 1) PubMed:8282104

Appears in Networks:
Annotations
Confidence
High

p(HGNC:CDK5) directlyIncreases p(HGNC:MAPT, pmod(Ph, Ser, 202)) View Subject | View Object

The reaction with the diagnostic antibodies (Fig. 4) is similar to the examples shown previously for cdk2 (Fig. 2), MAP kinase [8], or GSK-3 [26], indicating the phosphorylation of the SP motifs for which these antibodies are sensitive (serines 199, 202, 235, 396, 404; see Fig. 1) PubMed:8282104

Appears in Networks:
Annotations
Confidence
High

p(HGNC:CDK5) directlyIncreases p(HGNC:MAPT, pmod(Ph, Ser, 235)) View Subject | View Object

The reaction with the diagnostic antibodies (Fig. 4) is similar to the examples shown previously for cdk2 (Fig. 2), MAP kinase [8], or GSK-3 [26], indicating the phosphorylation of the SP motifs for which these antibodies are sensitive (serines 199, 202, 235, 396, 404; see Fig. 1) PubMed:8282104

Appears in Networks:
Annotations
Confidence
High

p(HGNC:CDK5) directlyIncreases p(HGNC:MAPT, pmod(Ph, Ser, 396)) View Subject | View Object

The reaction with the diagnostic antibodies (Fig. 4) is similar to the examples shown previously for cdk2 (Fig. 2), MAP kinase [8], or GSK-3 [26], indicating the phosphorylation of the SP motifs for which these antibodies are sensitive (serines 199, 202, 235, 396, 404; see Fig. 1) PubMed:8282104

Appears in Networks:
Annotations
Confidence
High

p(HGNC:CDK5) directlyIncreases p(HGNC:MAPT, pmod(Ph, Ser, 404)) View Subject | View Object

The reaction with the diagnostic antibodies (Fig. 4) is similar to the examples shown previously for cdk2 (Fig. 2), MAP kinase [8], or GSK-3 [26], indicating the phosphorylation of the SP motifs for which these antibodies are sensitive (serines 199, 202, 235, 396, 404; see Fig. 1) PubMed:8282104

Appears in Networks:
Annotations
Confidence
High

p(HGNC:CDK5) association a(GO:microtubule) View Subject | View Object

Fig. 5 shows that the 31 kDa kinase is included in the MAP fraction after three or more cycles of microtubule assembly (lanes l-6), and is also associated with PHFs (lane 7) PubMed:8282104

Appears in Networks:
Annotations
Confidence
High

p(HGNC:CDK5) association a(HBP:HBP00006) View Subject | View Object

Fig. 5 shows that the 31 kDa kinase is included in the MAP fraction after three or more cycles of microtubule assembly (lanes l-6), and is also associated with PHFs (lane 7) PubMed:8282104

Appears in Networks:
Annotations
Confidence
High

p(HGNC:CDK5) increases rxn(reactants(p(HGNC:MAPT)), products(p(HGNC:MAPT, pmod(Ph)))) View Subject | View Object

Thus, we now know three kinases, cdk5, MAP kinase, and GSK-3, all of which are present in neurons, which are capable of transforming tau into the Alzheimer-like state, and therefore could account for the pathological phosphorylation of tau in Alzheimer brains PubMed:8282104

Appears in Networks:
Annotations
Confidence
High
MeSH
Neurons

p(HGNC:CDK5) positiveCorrelation path(MESH:"Alzheimer Disease") View Subject | View Object

Thus, we now know three kinases, cdk5, MAP kinase, and GSK-3, all of which are present in neurons, which are capable of transforming tau into the Alzheimer-like state, and therefore could account for the pathological phosphorylation of tau in Alzheimer brains PubMed:8282104

Appears in Networks:
Annotations
Confidence
High
MeSH
Neurons

act(p(HGNC:CDK5)) directlyIncreases p(HGNC:MAPT, pmod(Ph)) View Subject | View Object

Phosphorylation of tau by the kinases GSK3b, Cdk5 and MARK2 is a major regulator of its microtubule interactions PubMed:21882945

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p(HGNC:CDK5) increases act(p(HGNC:MARK2)) View Subject | View Object

Importantly, MARK2-based phosphorylation of tau is accelerated by the priming activity of either Cdk5 or GSK3b [29], suggesting that tau phosphorylation involves a series of ordered kinase events. PubMed:21882945

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act(p(HGNC:CDK5)) positiveCorrelation p(HGNC:CDC37) View Subject | View Object

Western blot analysis for a panel of tau kinases showed that only the levels of endogenous Cdk5 and Akt were significantly reduced by Cdc37 siRNA; the levels of GSK3-Beta and Mark2 (microtubule affinity regulating kinase 2) were largely unchanged PubMed:21367866

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p(HGNC:CDK5) increases p(HGNC:CAMKV, pmod(Ph, Thr, 345)) View Subject | View Object

However, co-expression of the phospho-mimetic T345E failed to restore the defects in spine density after CaMKv depletion (Fig. 4l,m), suggesting that CaMKv phosphorylation by Cdk5 at Thr345 inhibits its function. PubMed:27796283

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act(p(HGNC:CDK5)) increases p(HGNC:MAPT, pmod(Ph, Thr, 181)) View Subject | View Object

Here, we found that prephosphorylation by PKA promotes GSK-3beta-catalyzed tau phosphorylation at Thr181, Ser199, Ser202, Thr205, Thr217, Thr231, Ser396 and Ser422, but inhibits its phosphorylation at Thr212 and Ser404. In contrast, the prephosphorylation had no significant effect on its subsequent phosphorylation by cdk5 at Thr181, Ser199, Thr205, Thr231 and Ser422; inhibited it at Ser202, Thr212, Thr217 and Ser404; and slightly promoted it at Ser396. PubMed:17078951

Appears in Networks:

act(p(HGNC:CDK5)) increases p(HGNC:MAPT, pmod(Ph, Ser, 199)) View Subject | View Object

Here, we found that prephosphorylation by PKA promotes GSK-3beta-catalyzed tau phosphorylation at Thr181, Ser199, Ser202, Thr205, Thr217, Thr231, Ser396 and Ser422, but inhibits its phosphorylation at Thr212 and Ser404. In contrast, the prephosphorylation had no significant effect on its subsequent phosphorylation by cdk5 at Thr181, Ser199, Thr205, Thr231 and Ser422; inhibited it at Ser202, Thr212, Thr217 and Ser404; and slightly promoted it at Ser396. PubMed:17078951

Appears in Networks:

act(p(HGNC:CDK5)) increases p(HGNC:MAPT, pmod(Ph, Thr, 205)) View Subject | View Object

Here, we found that prephosphorylation by PKA promotes GSK-3beta-catalyzed tau phosphorylation at Thr181, Ser199, Ser202, Thr205, Thr217, Thr231, Ser396 and Ser422, but inhibits its phosphorylation at Thr212 and Ser404. In contrast, the prephosphorylation had no significant effect on its subsequent phosphorylation by cdk5 at Thr181, Ser199, Thr205, Thr231 and Ser422; inhibited it at Ser202, Thr212, Thr217 and Ser404; and slightly promoted it at Ser396. PubMed:17078951

Appears in Networks:

act(p(HGNC:CDK5)) increases p(HGNC:MAPT, pmod(Ph, Thr, 231)) View Subject | View Object

Here, we found that prephosphorylation by PKA promotes GSK-3beta-catalyzed tau phosphorylation at Thr181, Ser199, Ser202, Thr205, Thr217, Thr231, Ser396 and Ser422, but inhibits its phosphorylation at Thr212 and Ser404. In contrast, the prephosphorylation had no significant effect on its subsequent phosphorylation by cdk5 at Thr181, Ser199, Thr205, Thr231 and Ser422; inhibited it at Ser202, Thr212, Thr217 and Ser404; and slightly promoted it at Ser396. PubMed:17078951

Appears in Networks:

act(p(HGNC:CDK5)) increases p(HGNC:MAPT, pmod(Ph, Ser, 422)) View Subject | View Object

Here, we found that prephosphorylation by PKA promotes GSK-3beta-catalyzed tau phosphorylation at Thr181, Ser199, Ser202, Thr205, Thr217, Thr231, Ser396 and Ser422, but inhibits its phosphorylation at Thr212 and Ser404. In contrast, the prephosphorylation had no significant effect on its subsequent phosphorylation by cdk5 at Thr181, Ser199, Thr205, Thr231 and Ser422; inhibited it at Ser202, Thr212, Thr217 and Ser404; and slightly promoted it at Ser396. PubMed:17078951

Appears in Networks:

act(p(HGNC:CDK5)) increases complex(p(HGNC:CDK5), p(HGNC:MAPT, pmod(Ph, Ser, 202))) View Subject | View Object

Here, we found that prephosphorylation by PKA promotes GSK-3beta-catalyzed tau phosphorylation at Thr181, Ser199, Ser202, Thr205, Thr217, Thr231, Ser396 and Ser422, but inhibits its phosphorylation at Thr212 and Ser404. In contrast, the prephosphorylation had no significant effect on its subsequent phosphorylation by cdk5 at Thr181, Ser199, Thr205, Thr231 and Ser422; inhibited it at Ser202, Thr212, Thr217 and Ser404; and slightly promoted it at Ser396. PubMed:17078951

Appears in Networks:

act(p(HGNC:CDK5)) increases complex(p(HGNC:CDK5), p(HGNC:MAPT, pmod(Ph, Thr, 212))) View Subject | View Object

Here, we found that prephosphorylation by PKA promotes GSK-3beta-catalyzed tau phosphorylation at Thr181, Ser199, Ser202, Thr205, Thr217, Thr231, Ser396 and Ser422, but inhibits its phosphorylation at Thr212 and Ser404. In contrast, the prephosphorylation had no significant effect on its subsequent phosphorylation by cdk5 at Thr181, Ser199, Thr205, Thr231 and Ser422; inhibited it at Ser202, Thr212, Thr217 and Ser404; and slightly promoted it at Ser396. PubMed:17078951

Appears in Networks:

act(p(HGNC:CDK5)) increases complex(p(HGNC:CDK5), p(HGNC:MAPT, pmod(Ph, Thr, 217))) View Subject | View Object

Here, we found that prephosphorylation by PKA promotes GSK-3beta-catalyzed tau phosphorylation at Thr181, Ser199, Ser202, Thr205, Thr217, Thr231, Ser396 and Ser422, but inhibits its phosphorylation at Thr212 and Ser404. In contrast, the prephosphorylation had no significant effect on its subsequent phosphorylation by cdk5 at Thr181, Ser199, Thr205, Thr231 and Ser422; inhibited it at Ser202, Thr212, Thr217 and Ser404; and slightly promoted it at Ser396. PubMed:17078951

Appears in Networks:

act(p(HGNC:CDK5)) increases complex(p(HGNC:CDK5), p(HGNC:MAPT, pmod(Ph, Ser, 404))) View Subject | View Object

Here, we found that prephosphorylation by PKA promotes GSK-3beta-catalyzed tau phosphorylation at Thr181, Ser199, Ser202, Thr205, Thr217, Thr231, Ser396 and Ser422, but inhibits its phosphorylation at Thr212 and Ser404. In contrast, the prephosphorylation had no significant effect on its subsequent phosphorylation by cdk5 at Thr181, Ser199, Thr205, Thr231 and Ser422; inhibited it at Ser202, Thr212, Thr217 and Ser404; and slightly promoted it at Ser396. PubMed:17078951

Appears in Networks:

act(p(HGNC:CDK5)) increases complex(p(HGNC:CDK5), p(HGNC:MAPT, pmod(Ph, Ser, 396))) View Subject | View Object

Here, we found that prephosphorylation by PKA promotes GSK-3beta-catalyzed tau phosphorylation at Thr181, Ser199, Ser202, Thr205, Thr217, Thr231, Ser396 and Ser422, but inhibits its phosphorylation at Thr212 and Ser404. In contrast, the prephosphorylation had no significant effect on its subsequent phosphorylation by cdk5 at Thr181, Ser199, Thr205, Thr231 and Ser422; inhibited it at Ser202, Thr212, Thr217 and Ser404; and slightly promoted it at Ser396. PubMed:17078951

Appears in Networks:

act(p(HGNC:CDK5)) increases p(HGNC:SYN1, pmod(Ph, Ser, 551)) View Subject | View Object

The phosphorylation sites were determined to be Ser551 and Ser553 with Cdk5-p23, and Ser62, Ser67, and Ser551 with MAP kinase. Upon phosphorylation with MAP kinase, synapsin I showed reduced F-actin bundling activity, while no significant effect on the interaction was observed with the protein phosphorylated with Cdk5-p23. PubMed:8702879

Appears in Networks:

act(p(HGNC:CDK5)) increases p(HGNC:SYN1, pmod(Ph, Ser, 553)) View Subject | View Object

The phosphorylation sites were determined to be Ser551 and Ser553 with Cdk5-p23, and Ser62, Ser67, and Ser551 with MAP kinase. Upon phosphorylation with MAP kinase, synapsin I showed reduced F-actin bundling activity, while no significant effect on the interaction was observed with the protein phosphorylated with Cdk5-p23. PubMed:8702879

Appears in Networks:

p(HGNC:CDK5) increases complex(p(HGNC:CDK5), p(HGNC:CDK5R1)) View Subject | View Object

To perform its function, Cdk5 must bind to the neuron-specific regulatory subunit protein p35, which is beneficial for neuronal development (Tsai et al. 1994; Chae et al. 1997). However, truncation of p35 and conversion to p25 (Patrick et al. 1999) is found in the forebrain of rats after focal cerebral ischemia and in AD patients, and these alterations are deleterious to the brain PubMed:26118667

Appears in Networks:

act(p(HGNC:CDK5), ma(kin)) directlyIncreases p(HGNC:MAPT, pmod(HBP:hyperphosphorylation)) View Subject | View Object

In primary neurons, overexpression of miR-125b causes tau hyperphosphorylation and an upregulation of p35, cdk5, and p44/42-MAPK signaling. In parallel, the phosphatases DUSP6 and PPP1CA and the anti-apoptotic factor Bcl-W are downregulated as direct targets of miR-125b. Knockdown of these phosphatases induces tau hyperphosphorylation, and overexpression of PPP1CA and Bcl-W prevents miR-125b-induced tau phosphorylation, suggesting that they mediate the effects of miR-125b on tau. Conversely, suppression of miR-125b in neurons by tough decoys reduces tau phosphorylation and kinase expression/activity. Injecting miR-125b into the hippocampus of mice impairs associative learning and is accompanied by downregulation of Bcl-W, DUSP6, and PPP1CA, resulting in increased tau phosphorylation in vivo. Importantly, DUSP6 and PPP1CA are also reduced in AD brains. PubMed:25001178

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act(p(HGNC:CDK5), ma(kin)) positiveCorrelation act(p(HGNC:MAPK1), ma(kin)) View Subject | View Object

Since Erk1/2 activity has been shown to induce cdk5 (Harada et al, 2001), miR-125b-induced Erk1/2 activation through DUSP6 downregulation might ultimately stimulate aberrant cdk5/p35 activation and, consequently, enhance pathological tau phosphorylation at multiple sites PubMed:25001178

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p(HGNC:CDK5) increases p(HGNC:MAPT, pmod(Ph)) View Subject | View Object

Pro-inflammatory IL-18 increases AD-associated A beta deposition in human neuron-like cells in culture [55]. IL-18 also increases the expression of glycogen synthase kinase 3 beta (GSK-3 beta ) and cyclin-dependent kinase 5, both of which are involved in hyperphos- phorylation of the tau protein [56]. PubMed:27314526

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Annotations
Confidence
High
MeSH
Alzheimer Disease
NeuroMMSigDB
Amyloidogenic subgraph
NeuroMMSigDB
Cyclin-CDK subgraph
NeuroMMSigDB
GSK3 subgraph
NeuroMMSigDB
Interleukin signaling subgraph
NeuroMMSigDB
Tau protein subgraph

p(HGNC:CDK5) positiveCorrelation path(MESH:"Alzheimer Disease") View Subject | View Object

Inactivation of Prdx-2 is controlled by a kinase that has been shown to be elevated in AD, CDK5, 107, 108 which phosphorylates Thr 89 and results in deactivation of Prdx-2. PubMed:30444369

Appears in Networks:
Annotations
MeSH
Neurons

p(HGNC:CDK5) increases p(HGNC:PRDX2, pmod(Ph, Thr, 89)) View Subject | View Object

Inactivation of Prdx-2 is controlled by a kinase that has been shown to be elevated in AD, CDK5, 107, 108 which phosphorylates Thr 89 and results in deactivation of Prdx-2. PubMed:30444369

Appears in Networks:
Annotations
MeSH
Neurons

p(HGNC:CDK5) association path(MESH:"Alzheimer Disease") View Subject | View Object

PP2A enzymes can also associate with protein kinases that have been linked to AD, such as glycogen synthase kinase 3β (GSK3β) and cyclin-dependent kinase 5 (cdk5; Plattner et al.,2006), and neuronal receptors, e.g., the NMDA receptor (Chan and Sucher, 2001) and the metabotropic glutamate receptor 5 (Mao et al., 2005; Arif et al., 2014). PubMed:24653673

Appears in Networks:

act(p(HGNC:CDK5)) negativeCorrelation a(GO:"microtubule cytoskeleton") View Subject | View Object

Apart from affecting tau phosphorylation, abnormal activation of GSK3β, cdk5, and ERK has been linked to cytoskeletal abnormalities (microtubules, neurofilaments), alterations in amyloid precursor protein (APP) phosphorylation and processing, impairment of neurogenesis, alterations in synaptic plasticity and induction of apoptotic processes (Reviewed in Crews and Masliah, 2010; Medina and Avila, 2013, 2014). PubMed:24653673

Appears in Networks:

act(p(HGNC:CDK5)) negativeCorrelation a(GO:"neurofilament cytoskeleton") View Subject | View Object

Apart from affecting tau phosphorylation, abnormal activation of GSK3β, cdk5, and ERK has been linked to cytoskeletal abnormalities (microtubules, neurofilaments), alterations in amyloid precursor protein (APP) phosphorylation and processing, impairment of neurogenesis, alterations in synaptic plasticity and induction of apoptotic processes (Reviewed in Crews and Masliah, 2010; Medina and Avila, 2013, 2014). PubMed:24653673

Appears in Networks:

act(p(HGNC:CDK5)) negativeCorrelation p(HGNC:APP, pmod(Ph)) View Subject | View Object

Apart from affecting tau phosphorylation, abnormal activation of GSK3β, cdk5, and ERK has been linked to cytoskeletal abnormalities (microtubules, neurofilaments), alterations in amyloid precursor protein (APP) phosphorylation and processing, impairment of neurogenesis, alterations in synaptic plasticity and induction of apoptotic processes (Reviewed in Crews and Masliah, 2010; Medina and Avila, 2013, 2014). PubMed:24653673

Appears in Networks:

act(p(HGNC:CDK5)) negativeCorrelation bp(HBP:"APP processing") View Subject | View Object

Apart from affecting tau phosphorylation, abnormal activation of GSK3β, cdk5, and ERK has been linked to cytoskeletal abnormalities (microtubules, neurofilaments), alterations in amyloid precursor protein (APP) phosphorylation and processing, impairment of neurogenesis, alterations in synaptic plasticity and induction of apoptotic processes (Reviewed in Crews and Masliah, 2010; Medina and Avila, 2013, 2014). PubMed:24653673

Appears in Networks:

act(p(HGNC:CDK5)) negativeCorrelation bp(GO:neurogenesis) View Subject | View Object

Apart from affecting tau phosphorylation, abnormal activation of GSK3β, cdk5, and ERK has been linked to cytoskeletal abnormalities (microtubules, neurofilaments), alterations in amyloid precursor protein (APP) phosphorylation and processing, impairment of neurogenesis, alterations in synaptic plasticity and induction of apoptotic processes (Reviewed in Crews and Masliah, 2010; Medina and Avila, 2013, 2014). PubMed:24653673

Appears in Networks:

act(p(HGNC:CDK5)) positiveCorrelation bp(GO:"negative regulation of synaptic plasticity") View Subject | View Object

Apart from affecting tau phosphorylation, abnormal activation of GSK3β, cdk5, and ERK has been linked to cytoskeletal abnormalities (microtubules, neurofilaments), alterations in amyloid precursor protein (APP) phosphorylation and processing, impairment of neurogenesis, alterations in synaptic plasticity and induction of apoptotic processes (Reviewed in Crews and Masliah, 2010; Medina and Avila, 2013, 2014). PubMed:24653673

Appears in Networks:

act(p(HGNC:CDK5)) positiveCorrelation bp(GO:"apoptotic process") View Subject | View Object

Apart from affecting tau phosphorylation, abnormal activation of GSK3β, cdk5, and ERK has been linked to cytoskeletal abnormalities (microtubules, neurofilaments), alterations in amyloid precursor protein (APP) phosphorylation and processing, impairment of neurogenesis, alterations in synaptic plasticity and induction of apoptotic processes (Reviewed in Crews and Masliah, 2010; Medina and Avila, 2013, 2014). PubMed:24653673

Appears in Networks:

p(HGNC:CDK5) increases p(HGNC:MAPT, pmod(Ph)) View Subject | View Object

Among the specific “proline-dependent” kinases that can phosphorylate protein tau at dif- ferent sites in vitro, special attention is dedicated to glycogen-synthase kinase-3β (GSK-3β) (Michel et al., 1998), mitogen-activated protein kinase (MAPK) (Drewes et al., 1992), stress-activated protein kinases (SAPKs) (Goedert et al., 1997) and cyclin-dependent kinases (CDKs) including cdc2 and cdk5 (Baumann et al., 1993; Patrick et al., 1999). PubMed:12428809

Appears in Networks:

p(HGNC:CDK5) increases p(HGNC:MAPT, pmod(Ph)) View Subject | View Object

Tau phosphorylation, the major disease-related post-translational modification, is highly regulated by glycogen synthase kinase-3β (GSK-3β), cyclin-dependent kinase 5 (CDK5), mitogen-activated protein kinase (MAPK) and other kinases. PubMed:29758300

Appears in Networks:

p(HGNC:CDK5) directlyIncreases p(HGNC:MAPT, pmod(Ph)) View Subject | View Object

The responsible kinases include 1) proline-directed protein kinases (PDPKs) targeting SP or TP motifs [e.g., GSK3b, cyclindependent kinase (CDK)-5, and MAPKs]; 2) non–proline directed protein kinases targeting KXGS-motifs [e.g., PKA, microtubule affinity-regulating kinase and synapses of the amphid defective (SADK)]; 3) protein kinases specific for tyrosines (e.g., Src, Lck, Syk, Fyn, and c-Abl kinase) (91). PubMed:29191965

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p(HGNC:CDK5) regulates p(HGNC:DPYSL2) View Subject | View Object

In line with this, the dendritic spine-regulating activity of CRMP2 is under the control of the cyclin-dependent kinase 5 (CDK5) PubMed:30061532

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p(HGNC:CDK5) positiveCorrelation a(GO:"dendritic spine") View Subject | View Object

Both administration of amphetamines and stimulation of D1R induce a significant increase of CDK5 gene expression and protein levels, which, at molecular level, associates with increased dendritic spine density and hyper-phosphorylation of the cytoskeletal tau protein PubMed:30061532

Appears in Networks:

p(HGNC:CDK5) positiveCorrelation p(HGNC:MAPT, pmod(HBP:hyperphosphorylation)) View Subject | View Object

Both administration of amphetamines and stimulation of D1R induce a significant increase of CDK5 gene expression and protein levels, which, at molecular level, associates with increased dendritic spine density and hyper-phosphorylation of the cytoskeletal tau protein PubMed:30061532

Appears in Networks:

act(p(HGNC:CDK5)) positiveCorrelation path(MESH:Schizophrenia) View Subject | View Object

Remarkably, the marked reduction of p35 levels in schizophrenic brains, which mirrors enhanced CDK5 activity [247], suggests a role for CDK5-CRMP2-dependent alterations of cytoskeleton architecture and psychiatric behavior PubMed:30061532

Appears in Networks:
Annotations
MeSH
Brain

act(p(HGNC:CDK5)) negativeCorrelation p(HGNC:CDK5R1) View Subject | View Object

Remarkably, the marked reduction of p35 levels in schizophrenic brains, which mirrors enhanced CDK5 activity [247], suggests a role for CDK5-CRMP2-dependent alterations of cytoskeleton architecture and psychiatric behavior PubMed:30061532

Appears in Networks:
Annotations
MeSH
Brain

About

BEL Commons is developed and maintained in an academic capacity by Charles Tapley Hoyt and Daniel Domingo-Fernández at the Fraunhofer SCAI Department of Bioinformatics with support from the IMI project, AETIONOMY. It is built on top of PyBEL, an open source project. Please feel free to contact us here to give us feedback or report any issues. Also, see our Publishing Notes and Data Protection information.

If you find BEL Commons useful in your work, please consider citing: Hoyt, C. T., Domingo-Fernández, D., & Hofmann-Apitius, M. (2018). BEL Commons: an environment for exploration and analysis of networks encoded in Biological Expression Language. Database, 2018(3), 1–11.