Integrin-linked kinase (ILK) is a multifunctional molecular actor in cell-matrix interactions, cell adhesion, and anchorage-dependent cell growth. It combines functions of a signal transductor and a scaffold protein through its interaction with integrins, then facilitating further protein recruitment within the ILK-PINCH-Parvin complex. ILK is involved in crucial cellular processes including proliferation, survival, differentiation, migration, invasion, and angiogenesis, which reflects on systemic changes in the kidney, heart, muscle, skin, and vascular system, also during the embryonal development. Dysfunction of ILK underlies the pathogenesis of various diseases, including the pro-oncogenic activity in tumorigenesis. ILK localizes mostly to the cell membrane and remains an important component of focal adhesion. We do know much about ILK but a lot still remains either uncovered or unclear. Although it was initially classified as a serine/threonine-protein kinase, its catalytical activity is now questioned due to structural and functional issues, leaving the exact molecular mechanism of signal transduction by ILK unsolved. While it is known that the three isoforms of ILK vary in length, the presence of crucial domains, and modification sites, most of the research tends to focus on the main isoform of this protein while the issue of functional differences of ILK2 and ILK3 still awaits clarification. The activity of ILK is regulated on the transcriptional, protein, and post-transcriptional levels. The crucial role of phosphorylation and ubiquitylation has been investigated, but the functions of the vast majority of modifications are still unknown. In the light of all those open issues, here we present an extensive literature survey covering a wide spectrum of latest findings as well as a past-to-present view on controversies regarding ILK, finishing with pointing out some open questions to be resolved by further research.
Keywords: Cancer; Cell adhesion; Development; Epithelial-mesenchymal transition (EMT); Exosomes/extracellular vesicles; Integrin-linked kinase (ILK); Migration; Multidrug resistance (MDR); Signaling.
© 2022. The Author(s).