Integrin Cell Signaling Pathway Transduction

Integrins can mediate cell signaling transduction by two mechanisms, so called “inside out” signaling and “outside in” signaling.

Inside out signaling is the mechanism by which a cell regulates the affinity state of its integrin receptors. It is thought to involve the propagation of conformational changes from the cytoplasmic domains of integrins to the extracellular binding site in response to intracellular signaling events.

Several regions within the cytoplasmic domains of both α and β subunits have been shown to be involved in regulating the affinity state of the integrin receptor.

There is evidence that conformational changes within these regions, brought about through phosphorylation or dephosphorylation events, allow the association of other proteins that can regulate the integrin activity state.

Outside in signaling mediates signals from the extracellular matrix after integrin ligation and involves regulation of many fundamental cellular processes.

It involves integrin–ligand binding and receptor clustering, with subsequent assembly of the focal adhesion plaque—a complex of cytoskeletal proteins and signaling molecules including paxillin, talin, vinculin, α-actinin, tensin, and focal adhesion kinase (FAK).

This process is dependent on the GTPase Rho A. Phosphorylated FAK can also lead to activation of the mitogen activated protein (MAP) kinase pathway, probably via Ras activation, which can then influence gene expression.