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Integrin-linked kinase: Not so ‘pseudo’ after all

Oncogene volume 30, pages 4375–4385 (2011)Cite this article

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Abstract

Integrin-linked kinase (ILK) is a highly evolutionarily conserved intracellular protein that was originally identified as an integrin-interacting protein, and extensive genetic and biochemical studies have shown that ILK expression is vital during both embryonic development and tissue homeostasis. At the cellular and tissue levels, ILK regulates signaling pathways for cell adhesion-mediated cell survival (anoikis), apoptosis, proliferation and mitosis, migration, invasion, and vascularization and tumor angiogenesis. ILK also has central roles in cardiac and smooth-muscle contractility, and ILK dysregulation causes cardiomyopathies in humans. ILK protein levels are increased in several human cancers and often the expression level predicts poor patient outcome. Abundant evidence has accumulated suggesting that, of the diverse functions of ILK, some may require kinase activity whereas others depend on protein–protein interactions and are, therefore, independent of kinase activity. However, the past several years have seen an ongoing debate about whether ILK indeed functions as a protein serine/threonine kinase. This debate centers on the atypical protein kinase domain of ILK, which lacks some amino-acid residues thought to be essential for phosphotransferase activity. However, similar deficiencies are present in the catalytic domains of other kinases now known to possess protein kinase activity. Numerous studies have shown that ILK phosphorylates peptide substrates in vitro, corresponding to ILK-mediated phosphorylations in intact cells, and a recent report characterizing in vitro phosphotransferase activity of highly purified, full-length ILK, accompanied by detailed enzyme kinetic analyses, shows that, at least in vitro, ILK is a bona fide protein kinase. However, several genetic studies suggest that, not all biological functions of ILK require kinase activity, and that it can function as an adaptor/scaffold protein. Here, we review evidence for and against ILK being an active kinase, and provide a framework for strategies to further analyze the kinase and adaptor functions of ILK in different cellular contexts.

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Acknowledgements

This work was supported by funding from the Canadian Institutes of Health Research (to SD and MPW), the Canadian Cancer Society Research Institute (to SD) and the National Health and Medical Research Council (NHMRC) of Australia (to GEH).

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Authors and Affiliations

  1. Centre for Cancer Research, Monash Institute of Medical Research, Melbourne, Victoria, Australia

    G E Hannigan

  2. Department of Integrative Oncology, BC Cancer Research Centre, Vancouver, British Columbia, Canada

    P C McDonald & S Dedhar

  3. Department of Biochemistry and Molecular Biology, University of Calgary, Calgary, Alberta, Canada

    M P Walsh

  4. Department of Biochemistry and Molecular Biology, University of British Columbia, Vancouver, British Columbia, Canada

    S Dedhar

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Hannigan, G., McDonald, P., Walsh, M. et al. Integrin-linked kinase: Not so ‘pseudo’ after all. Oncogene 30, 4375–4385 (2011). https://doi.org/10.1038/onc.2011.177

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