Page last updated: 2024-10-24

regulation of protein serine/threonine kinase activity

Definition

Target type: biologicalprocess

Any process that modulates the rate, frequency, or extent of protein serine/threonine kinase activity. [GOC:mah]

Regulation of protein serine/threonine kinase activity is a fundamental biological process that governs the phosphorylation of serine and threonine residues within proteins. This phosphorylation can significantly alter protein activity, localization, and interactions, playing a crucial role in a vast array of cellular functions.

Here's a detailed breakdown of the process:

**1. Kinase Activation:**

* **Upstream Signals:** Regulation begins with upstream signals, often originating from extracellular stimuli such as growth factors, hormones, or stress. These signals activate a cascade of intracellular signaling events, ultimately leading to the activation of protein kinases.
* **Activation Mechanisms:** Kinases can be activated through various mechanisms, including:
* **Ligand Binding:** Binding of specific ligands to receptors can trigger signaling cascades that activate kinases.
* **Phosphorylation:** Kinases themselves can be phosphorylated by other kinases, leading to conformational changes and activation.
* **Protein-Protein Interactions:** Interactions with regulatory proteins can activate or inhibit kinase activity.

**2. Substrate Recognition and Phosphorylation:**

* **Substrate Specificity:** Kinases exhibit a high degree of substrate specificity, recognizing specific amino acid sequences or motifs within their target proteins. This specificity ensures that phosphorylation occurs at precise locations, leading to specific downstream effects.
* **Phosphorylation Process:** Once activated, kinases catalyze the transfer of a phosphate group from ATP to the hydroxyl group of a serine or threonine residue within the substrate protein. This phosphorylation event creates a phospho-serine or phospho-threonine residue, altering the protein's conformation and function.

**3. Downstream Effects and Signal Propagation:**

* **Functional Modulation:** Phosphorylation can have a diverse range of effects on target proteins:
* **Activation/Inhibition:** Phosphorylation can activate or inhibit protein activity, depending on the specific substrate and site of phosphorylation.
* **Localization:** Phosphorylation can alter a protein's localization within the cell, affecting its ability to interact with other proteins or access specific cellular compartments.
* **Protein-Protein Interactions:** Phosphorylation can create or disrupt protein-protein interactions, influencing the formation of signaling complexes or the assembly of protein complexes.

**4. Regulation of Kinase Activity:**

* **Negative Feedback Loops:** Kinase activity is often regulated through negative feedback loops, where the downstream products of phosphorylation pathways can inhibit the activity of the kinases involved.
* **Protein Phosphatases:** Protein phosphatases are enzymes that remove phosphate groups from proteins, acting as counter-regulatory mechanisms to kinases.
* **Ubiquitination and Degradation:** Kinases can be targeted for degradation by ubiquitination, a process that tags proteins for proteasomal breakdown, thereby controlling their activity and levels.

**5. Aberrant Regulation in Disease:**

* **Cancer:** Aberrant regulation of protein kinase activity is a hallmark of many cancers. Mutations or overexpression of kinases can drive uncontrolled cell growth and proliferation.
* **Neurological Disorders:** Dysregulation of kinase activity is implicated in a variety of neurological disorders, including Alzheimer's disease, Parkinson's disease, and epilepsy.
* **Metabolic Disorders:** Kinases play crucial roles in regulating metabolic processes, and defects in kinase activity can contribute to disorders such as diabetes and obesity.

In summary, the regulation of protein serine/threonine kinase activity is a complex and intricate process involving multiple layers of control. This process is essential for maintaining cellular homeostasis and orchestrating a wide range of physiological functions. Aberrant regulation of kinase activity can lead to a variety of diseases, highlighting the importance of understanding these signaling pathways.'
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Proteins (1)

ProteinDefinitionTaxonomy
NAD-dependent protein deacetylase sirtuin-1An NAD-dependent protein deacetylase sirtuin-1 that is encoded in the genome of human. [PRO:DNx, UniProtKB:Q96EB6]Homo sapiens (human)

Compounds (33)

CompoundDefinitionClassesRoles
niacinamidenicotinamide : A pyridinecarboxamide that is pyridine in which the hydrogen at position 3 is replaced by a carboxamide group.pyridine alkaloid;
pyridinecarboxamide;
vitamin B3
anti-inflammatory agent;
antioxidant;
cofactor;
EC 2.4.2.30 (NAD(+) ADP-ribosyltransferase) inhibitor;
EC 3.5.1.98 (histone deacetylase) inhibitor;
Escherichia coli metabolite;
geroprotector;
human urinary metabolite;
metabolite;
mouse metabolite;
neuroprotective agent;
Saccharomyces cerevisiae metabolite;
Sir2 inhibitor
bisindolylmaleimide ibisindolylmaleimide I: a bis(indolyl)maleimide
bisindolylmaleimide vbisindolylmaleimide V: used as a negative control compound for protein kinase C inhibition; structure in first source;indoles
entinostatbenzamides;
carbamate ester;
primary amino compound;
pyridines;
substituted aniline
antineoplastic agent;
apoptosis inducer;
EC 3.5.1.98 (histone deacetylase) inhibitor
fenamic acidfenamic acid : An aminobenzoic acid that is the N-phenyl derivative of anthranilic acid. It acts as a parent skeleton for the synthesis of several non-steroidal anti-inflammatory drugs.

fenamic acid: has chloride and potassium channel-blocking activity; RN given refers to parent cpd
aminobenzoic acid;
secondary amino compound
membrane transport modulator
ro 31-8220Ro 31-8220: a protein kinase C inhibitorimidothiocarbamic ester;
indoles;
maleimides
EC 2.7.11.13 (protein kinase C) inhibitor
fenofibratebenzochromenone;
delta-lactone;
naphtho-alpha-pyrone
platelet aggregation inhibitor;
Sir2 inhibitor
suraminsuramin : A member of the class of phenylureas that is urea in which each of the amino groups has been substituted by a 3-({2-methyl-5-[(4,6,8-trisulfo-1-naphthyl)carbamoyl]phenyl}carbamoyl)phenyl group. An activator of both the rabbit skeletal muscle RyR1 and sheep cardiac RyR2 isoform ryanodine receptor channels, it has been used for the treatment of human African trypanosomiasis for over 100 years.

Suramin: A polyanionic compound with an unknown mechanism of action. It is used parenterally in the treatment of African trypanosomiasis and it has been used clinically with diethylcarbamazine to kill the adult Onchocerca. (From AMA Drug Evaluations Annual, 1992, p1643) It has also been shown to have potent antineoplastic properties.
naphthalenesulfonic acid;
phenylureas;
secondary carboxamide
angiogenesis inhibitor;
antinematodal drug;
antineoplastic agent;
apoptosis inhibitor;
EC 2.7.11.13 (protein kinase C) inhibitor;
GABA antagonist;
GABA-gated chloride channel antagonist;
purinergic receptor P2 antagonist;
ryanodine receptor agonist;
trypanocidal drug
nadNADgeroprotector
4-tert-butylbenzoic acid4-tert-butylbenzoic acid: RN given refers to parent cpdalkylbenzene
suramin sodiumsuramin sodium : An organic sodium salt that is the hexasodium salt of suramin. It is an FDA approved drug for African sleeping sickness and river blindness.organic sodium saltangiogenesis inhibitor;
antinematodal drug;
antineoplastic agent;
apoptosis inhibitor;
EC 2.7.11.13 (protein kinase C) inhibitor;
GABA antagonist;
GABA-gated chloride channel antagonist;
purinergic receptor P2 antagonist;
ryanodine receptor agonist;
trypanocidal drug
toxoflavintoxoflavin : A pyrimidotriazine that is 1,6-dimethyl-1,5,6,7-tetrahydropyrimido[5,4-e][1,2,4]triazine with oxo groups at positions 5 and 7.

toxoflavin: azapteridine antibiotic; structure
carbonyl compound;
pyrimidotriazine
antibacterial agent;
antineoplastic agent;
apoptosis inducer;
bacterial metabolite;
toxin;
virulence factor;
Wnt signalling inhibitor
paullonepaullone : An indolobenzazepine that is 5,6,7,12-tetrahydroindolo[3,2-d][1]benzazepine carrying an oxo substituent at position 6.

paullone: structure in first source
indolobenzazepine;
lactam
EC 2.7.11.22 (cyclin-dependent kinase) inhibitor;
EC 2.7.11.26 (tau-protein kinase) inhibitor
hyperforinhyperforin : A cyclic terpene ketone that is a prenylated carbobicyclic acylphloroglucinol derivative produced by St. John's Wort, Hypericum perforatum.

hyperforin: a prenylated acylphloroglucinol derivative; antibiotic component of novoimanine; psychoactive agent in St. John's wort; Russian; structure;
surfactin csurfactin C : A cyclodepsipeptide that is N-[(3R)-3-hydroxy-13-methyltetradecanoyl]-L-alpha-glutamyl-L-leucyl-D-leucyl-L-valyl-L-alpha-aspartyl-D-leucyl-L-leucine in which the C-terminal carboxy group has been lactonised by condensation with the alcoholic hydroxy group.cyclodepsipeptide;
lipopeptide antibiotic;
macrocyclic lactone
antibacterial agent;
antifungal agent;
antineoplastic agent;
antiviral agent;
metabolite;
platelet aggregation inhibitor;
surfactant
resveratroltrans-resveratrol : A resveratrol in which the double bond has E configuration.resveratrolantioxidant;
phytoalexin;
plant metabolite;
quorum sensing inhibitor;
radical scavenger
CHIC-35CHIC-35 : An organic heterotricyclic compound resulting from the formal fusion of the 2-3 bond of 5-chloroindole with the 2-3 bond of cycloheptanecarboxamide (the S enantiomer). It is a potent, cell-permeable, metabolically stable and selective inhibitor of the deacetylase SIRT1.aromatic compound;
organic heterotricyclic compound;
organochlorine compound;
primary carboxamide
EC 3.5.1.98 (histone deacetylase) inhibitor
3-(1-azepanylsulfonyl)-n-(3-bromphenyl)benzamide3-(1-azepanylsulfonyl)-N-(3-bromphenyl)benzamide: a sirtuin 2 inhibitor; structure in first source
CAY10591CAY10591: a SIRT1 NAD-dependent histone deacetylase activatorquinoxaline derivative
sirtinolaldimine;
benzamides;
naphthols
anti-inflammatory agent;
EC 3.5.1.98 (histone deacetylase) inhibitor;
Sir2 inhibitor
cambinolcambinol: inhibitor of human silent information regulator 2 enzymes; structure in first source
(4-chlorophenyl)-[4-(8-nitro-5-quinolinyl)-1-piperazinyl]methanoneN-arylpiperazine
ex 5276-chloro-2,3,4,9-tetrahydro-1H-carbazole-1-carboxamide : A member of the class of carbazoles that is 2,3,4,9-tetrahydro-1H-carbazole which is substituted at position 1 by an aminocarbohyl group and at position 6 by a chlorine.

6-chloro-2,3,4,9-tetrahydro-1H-carbazole-1-carboxamide: structure in first source
carbazoles;
monocarboxylic acid amide;
organochlorine compound
panobinostatpanobinostat : A hydroxamic acid obtained by formal condensation of the carboxy group of (2E)-3-[4-({[2-(2-methylindol-3-yl)ethyl]amino}methyl)phenyl]prop-2-enoic acid with the amino group of hydroxylamine. A histone deacetylase inhibitor used (as its lactate salt) in combination with bortezomib and dexamethasone for the treatment of multiple myeloma.

Panobinostat: An indole and hydroxamic acid derivative that acts as a HISTONE DEACETYLASE inhibitor. It is used as an antineoplastic agent in combination with BORTEZOMIB and DEXAMETHASONE for the treatment of MULTIPLE MYELOMA.
cinnamamides;
hydroxamic acid;
methylindole;
secondary amino compound
angiogenesis modulating agent;
antineoplastic agent;
EC 3.5.1.98 (histone deacetylase) inhibitor
oblongifolin coblongifolin C: has antineoplastic activity; isolated from Garcinia yunnanensis; structure in first source
quisinostatindoles
srt1460SRT1460: small molecule activator of SIRT1 as therapeutics for the treatment of type 2 diabetes; structure in first source
srt1720
srt2183SRT2183: small molecule activator of SIRT1 as therapeutics for the treatment of type 2 diabetes; structure in first source
tenovin-6tenovin-6 : A monocarboxylic acid amide obtained by formal condensation of the carboxy group of 5-(dimethylamino)pentanoic acid with the aromatic amino group of N-[(4-aminophenyl)carbamothioyl]-4-tert-butylbenzamide.monocarboxylic acid amide;
tertiary amino compound;
thioureas
antineoplastic agent;
p53 activator;
Sir2 inhibitor
acy-1215ricolinostat: an HDAC6 inhibitor; structure in first sourcepyrimidinecarboxylic acid
aristoforinAristoforin: derivative of hyperforin, is a potent anticancer agent; structure in first source
n-(3-((2-hydroxynaphthalen-1-ylmethylene)amino)phenyl)-2-phenylpropionamide