integrin activation

Definition

Target type: biologicalprocess

The aggregation, arrangement and bonding together of an integrin, a heterodimeric adhesion receptor formed by the non-covalent association of particular alpha and beta subunits, that lead to the increased affinity of the integrin for its extracellular ligands. [GOC:add, PMID:12213832, PMID:14754902]

Integrin activation is a critical process in cell adhesion, migration, and signaling. It involves a series of conformational changes that transition the integrin from an inactive to an active state. Here's a detailed description:

1. **Inactive State:** Integrins in their inactive state exist in a bent conformation. The α and β subunits are closely associated, and the ligand-binding site is buried, preventing interaction with extracellular matrix (ECM) proteins.

2. **Inside-Out Signaling:** Activation initiates from the intracellular domain of the β subunit. This can be triggered by various intracellular signals, such as growth factors, cytokines, or mechanical cues. These signals activate intracellular signaling pathways, which, in turn, lead to the recruitment of adaptor proteins and kinases.

3. **Conformational Changes:** Activation of the intracellular domain induces conformational changes that propagate through the integrin structure. This conformational change involves a straightening of the α and β subunits, exposing the ligand-binding site and creating a more extended conformation.

4. **Ligand Binding:** The exposed ligand-binding site on the α subunit can now interact with specific ECM proteins. This interaction is often highly specific, depending on the integrin subtype and its target ligand.

5. **Outside-In Signaling:** Ligand binding further stabilizes the active conformation of the integrin. This event triggers outside-in signaling, which activates intracellular signaling pathways involved in cell adhesion, migration, and differentiation.

6. **Cluster Formation:** Once activated, integrins often cluster together on the cell surface, forming focal adhesions. These structures provide a strong mechanical link between the cell and the ECM, allowing for cell motility and force transmission.

7. **Deactivation:** Integrin activation is a dynamic process. Integrins can be deactivated through various mechanisms, such as the removal of activating signals, the binding of inhibitory ligands, or the internalization of the integrin complex.

In summary, integrin activation involves a complex interplay of intracellular and extracellular signals, leading to a series of conformational changes that regulate cell adhesion, migration, and signaling.'
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Proteins (2)

Compounds (4)