Integrin-linked kinase

A) Full length protein sequence of Arabidopsis. B) 3D structures of ILK repeats. C) N-terminal is blue C-terminal is red. Shows the succession of secondary elements. D) Amino acid sequence of ILK.

Integrin-linked kinase (ILK) is a protein that plays a critical role in the cellular processes of cell adhesion, cell migration, and signal transduction. It is an important component of the cellular matrix and cellular signaling pathways that influence cell survival, cell cycle, and cell differentiation. ILK interacts with integrins, which are transmembrane receptors that facilitate cell-extracellular matrix adhesion, to mediate its effects on cells.

Function

ILK functions as an adaptor protein and a serine/threonine protein kinase, linking integrins to the actin cytoskeleton and various signaling pathways. This interaction is crucial for the regulation of gene expression, cell growth, and apoptosis. ILK is involved in the phosphoinositide 3-kinase (PI3K) pathway, where it contributes to the activation of protein kinase B (AKT), a key player in cell survival and proliferation. Through its kinase activity, ILK phosphorylates and activates downstream effectors, such as AKT and GSK-3β, influencing cell fate decisions.

Structure

The structure of ILK comprises three main domains: an N-terminal ankyrin repeat domain, a central pleckstrin homology (PH) domain, and a C-terminal kinase domain. The ankyrin repeat domain is involved in protein-protein interactions, particularly with integrins and other components of the focal adhesion complex. The PH domain mediates interactions with phospholipids in the cell membrane, which is essential for the localization of ILK to cellular membranes and its activation. The kinase domain is responsible for the catalytic activity of ILK, although there is debate about its intrinsic kinase activity.

Role in Disease

Aberrant regulation and expression of ILK have been implicated in various diseases, including cancer, cardiovascular diseases, and fibrosis. In cancer, overexpression of ILK contributes to tumor progression, invasion, and metastasis by promoting cell survival, angiogenesis, and epithelial-mesenchymal transition (EMT). In cardiovascular diseases, ILK is involved in the pathological remodeling of the heart and blood vessels. Its role in fibrosis is linked to its ability to mediate cell adhesion and migration, processes that are crucial in the development of fibrotic tissue.

Research and Therapeutic Potential

Given its central role in critical cellular processes and disease, ILK is a target of interest for therapeutic intervention. Small molecule inhibitors of ILK have been developed and are being explored as potential treatments for cancer and other diseases where ILK plays a pathogenic role. Research is ongoing to better understand the complex regulatory mechanisms of ILK and to develop more effective and specific inhibitors.