Target type: biologicalprocess
The stopping, prevention, or reduction in frequency, rate or extent of protein kinase activity as a result of regulating the phosphorylation status of that protein kinase. [GOC:jl]
Negative regulation of protein kinase activity by regulation of protein phosphorylation is a complex process that involves the modulation of protein kinase activity through the control of protein phosphorylation. Protein kinases are enzymes that catalyze the transfer of a phosphate group from a donor molecule, typically ATP, to a substrate protein. This phosphorylation event can alter the activity of the target protein, either activating or inhibiting its function.
In the context of negative regulation, phosphorylation of a protein kinase can lead to its inactivation. This can occur through several mechanisms:
1. **Direct inhibition:** Phosphorylation can directly block the active site of the kinase, preventing it from binding to its substrate.
2. **Conformational change:** Phosphorylation can induce a conformational change in the kinase, altering its structure and rendering it inactive.
3. **Recruitment of inhibitory proteins:** Phosphorylation can create a binding site for inhibitory proteins that interact with the kinase and prevent its activity.
4. **Targeting for degradation:** Phosphorylation can tag the kinase for degradation by the proteasome, effectively removing it from the cellular system.
The regulation of protein phosphorylation itself is a dynamic process involving a network of kinases, phosphatases, and signaling molecules. Kinases are responsible for adding phosphate groups, while phosphatases remove them. These opposing actions create a delicate balance that controls the phosphorylation state of target proteins. Signaling molecules, such as hormones, growth factors, and cytokines, can activate specific kinases or phosphatases, thereby influencing the phosphorylation status of downstream proteins.
In summary, negative regulation of protein kinase activity by regulation of protein phosphorylation is a crucial mechanism for maintaining cellular homeostasis. This process involves the phosphorylation of kinases, leading to their inactivation through various mechanisms. The dynamic interplay between kinases, phosphatases, and signaling molecules ensures precise control over protein phosphorylation, allowing for fine-tuning of cellular responses to diverse stimuli.'
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Protein | Definition | Taxonomy |
---|---|---|
Nucleophosmin | A nucleophosmin that is encoded in the genome of human. [PRO:DNx, UniProtKB:P06748] | Homo sapiens (human) |
Compound | Definition | Classes | Roles |
---|---|---|---|
imatinib | aromatic amine; benzamides; N-methylpiperazine; pyridines; pyrimidines | antineoplastic agent; apoptosis inducer; tyrosine kinase inhibitor | |
pd 173955 | PD 173955: inhibits src family-selective tyrosine kinase; structure in first source | aryl sulfide; dichlorobenzene; methyl sulfide; pyridopyrimidine | tyrosine kinase inhibitor |
ellagic acid | catechols; cyclic ketone; lactone; organic heterotetracyclic compound; polyphenol | antioxidant; EC 1.14.18.1 (tyrosinase) inhibitor; EC 2.3.1.5 (arylamine N-acetyltransferase) inhibitor; EC 2.4.1.1 (glycogen phosphorylase) inhibitor; EC 2.5.1.18 (glutathione transferase) inhibitor; EC 2.7.1.127 (inositol-trisphosphate 3-kinase) inhibitor; EC 2.7.1.151 (inositol-polyphosphate multikinase) inhibitor; EC 2.7.4.6 (nucleoside-diphosphate kinase) inhibitor; EC 2.7.7.7 (DNA-directed DNA polymerase) inhibitor; EC 5.99.1.2 (DNA topoisomerase) inhibitor; EC 5.99.1.3 [DNA topoisomerase (ATP-hydrolysing)] inhibitor; food additive; fungal metabolite; geroprotector; plant metabolite; skin lightening agent | |
bosutinib | 4-((2,4-dichloro-5-methoxyphenyl)amino)-6-methoxy-7-(3-(4-methyl-1-piperazinyl)propoxy)-3-quinolinecarbonitrile: a Src kinase inhibitor; structure in first source | aminoquinoline; aromatic ether; dichlorobenzene; N-methylpiperazine; nitrile; tertiary amino compound | antineoplastic agent; tyrosine kinase inhibitor |
crizotinib | crizotinib : A 3-[1-(2,6-dichloro-3-fluorophenyl)ethoxy]-5-[1-(piperidin-4-yl)pyrazol-4-yl]pyridin-2-amine that has R configuration at the chiral centre. The active enantiomer, it acts as a kinase inhibitor and is used for the treatment of patients with locally advanced or metastatic non-small cell lung cancer (NSCLC) Crizotinib: A piperidine and aminopyridine derivative that acts as an inhibitor of RECEPTOR PROTEIN-TYROSINE KINASES, including ANAPLASTIC LYMPHOMA KINASE (ALK) and HEPATOCYTE GROWTH FACTOR RECEPTOR (HGFR; c-Met). It is used in the treatment of NON-SMALL CELL LUNG CANCER. | 3-[1-(2,6-dichloro-3-fluorophenyl)ethoxy]-5-[1-(piperidin-4-yl)pyrazol-4-yl]pyridin-2-amine | antineoplastic agent; biomarker; EC 2.7.10.1 (receptor protein-tyrosine kinase) inhibitor |
ceritinib | ceritinib : A member of the class of aminopyrimidines that is 2,6-diamino-5-chloropyrimidine in which the amino groups at positions 2 and 6 are respectively carrying 2-methoxy-4-(piperidin-4-yl)-5-methylphenyl and 2-(isopropylsulfonyl)phenyl substituents. Used for the treatment of ALK-positive metastatic non-small cell lung cancer. ceritinib: an anaplastic lymphoma kinase inhibitor | aminopyrimidine; aromatic ether; organochlorine compound; piperidines; secondary amino compound; sulfone | antineoplastic agent; EC 2.7.10.1 (receptor protein-tyrosine kinase) inhibitor |