negative regulation of integrin activation

Definition

Target type: biologicalprocess

Any process that stops, prevents, or reduces the frequency, rate, or extent of integrin activation. [GOC:add]

Negative regulation of integrin activation is a critical process that fine-tunes cell adhesion, migration, and signaling. Integrins, transmembrane receptors that connect the extracellular matrix to the cytoskeleton, are activated through a conformational change that exposes their ligand binding site. This activation is tightly controlled to prevent inappropriate adhesion and signaling. Several mechanisms are employed to negatively regulate integrin activation, including:

1. **Intracellular signaling pathways:**
* **Phosphorylation:** Specific kinases, such as focal adhesion kinase (FAK), Src family kinases, and protein kinase C (PKC), can phosphorylate integrin cytoplasmic tails or associated proteins, promoting integrin inactivation and preventing ligand binding.
* **GTPase activity:** Rho GTPases, particularly RhoA, are involved in regulating integrin activation. RhoA activation can lead to integrin clustering and activation, while RhoA inhibition can result in integrin inactivation.
* **Calcium signaling:** Increased intracellular calcium levels can trigger pathways that negatively regulate integrin activation, promoting detachment from the extracellular matrix.

2. **Cytoskeletal interactions:**
* **Actin dynamics:** Proper actin polymerization is essential for integrin activation. Disruption of actin filaments, such as through the action of cofilin or gelsolin, can lead to integrin inactivation.
* **Myosin activity:** Myosin motors contribute to integrin clustering and activation. Inhibition of myosin activity can negatively regulate integrin activation.

3. **Extracellular factors:**
* **Ligand binding:** The presence of certain extracellular ligands can promote integrin inactivation, for example, by triggering conformational changes that mask the ligand binding site.
* **Extracellular matrix components:** The composition and organization of the extracellular matrix can influence integrin activation. For example, the presence of certain ECM proteins or specific matrix stiffness can promote or inhibit integrin activation.

4. **Membrane trafficking:**
* **Endocytosis:** Integrins can be internalized through endocytosis, removing them from the cell surface and preventing further activation.
* **Recycling:** Internalized integrins can be recycled back to the cell surface, but this process is often regulated to control integrin activity.

These various mechanisms work in concert to ensure that integrin activation is carefully regulated, preventing excessive adhesion, promoting cell migration, and allowing cells to respond appropriately to their environment.'
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Proteins (2)

Compounds (21)