negative regulation of kinase activity

Definition

Target type: biologicalprocess

Any process that stops, prevents, or reduces the frequency, rate or extent of kinase activity, the catalysis of the transfer of a phosphate group, usually from ATP, to a substrate molecule. [GOC:mah]

Negative regulation of kinase activity is a crucial cellular process that modulates the activity of kinases, enzymes that catalyze the transfer of a phosphate group from a donor molecule to a substrate. Kinases play pivotal roles in various signaling pathways, controlling cellular processes like cell growth, differentiation, metabolism, and apoptosis. Deregulation of kinase activity is implicated in various diseases, including cancer, cardiovascular disease, and neurodegenerative disorders.

There are multiple mechanisms by which kinase activity can be negatively regulated. These include:

1. **Inhibitory proteins:** Specific proteins can bind to kinases and block their active sites, preventing substrate binding and phosphorylation. For example, protein kinases inhibitors (PKIs) are a family of proteins that directly bind to and inhibit specific kinase families.

2. **Phosphorylation:** Kinases themselves can be phosphorylated at specific residues, which can either activate or inhibit their activity. This phosphorylation can be mediated by other kinases or phosphatases.

3. **Degradation:** Kinases can be targeted for degradation by the ubiquitin-proteasome system. This process involves the attachment of ubiquitin molecules to the kinase, marking it for proteolytic breakdown.

4. **Localization:** The subcellular localization of kinases can influence their activity. For example, kinases may be sequestered in specific compartments, preventing their interaction with substrates.

5. **Competitive inhibitors:** Small molecule inhibitors can bind to the active site of kinases, competing with substrates for binding and blocking their activity. These inhibitors are often used as therapeutic agents to target specific kinases involved in disease processes.

6. **Allosteric regulation:** Kinases can be regulated by allosteric mechanisms, where the binding of a molecule to a site distinct from the active site affects the enzyme's activity. This modulation can either enhance or inhibit kinase activity.

7. **Feedback loops:** Negative feedback loops can regulate kinase activity, where the product of a kinase-mediated reaction inhibits the kinase itself, creating a self-regulating system.

8. **MicroRNAs:** MicroRNAs can target kinase mRNAs, leading to their degradation or translational inhibition, reducing kinase protein levels and activity.

9. **Protein-protein interactions:** Interactions with other proteins can modulate kinase activity, either by promoting activation or inhibition.

10. **Cellular stress:** Cells can respond to various stresses by regulating kinase activity. For example, stress-activated kinases can be activated to promote survival pathways or induce apoptosis depending on the type and severity of stress.

These diverse mechanisms ensure that kinase activity is tightly regulated, allowing cells to respond appropriately to various signals and maintain homeostasis.'
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Proteins (1)

Compounds (18)