Trends in Cell Biology
ReviewIntegrin-linked kinase (ILK): a regulator of integrin and growth-factor signalling
Section snippets
ILK structure and function
ILK contains three identifiable structural features (Fig. 1). There are four ankyrin repeats in the N-terminus. These are followed by a phosphoinositide-binding motif9 normally present in pleckstrin-homology (PH) domains7. This motif overlaps with the extreme N-terminus of the kinase catalytic domain (Fig. 1). In vitro kinase assays using recombinant ILK, and immunoprecipitation kinase assays in mammalian cell extracts, have revealed that ILK is a functional serine/threonine protein kinase
ILK genetics
ILK is highly evolutionarily conserved: there are ILK homologues in human2, mouse15, Drosophila (D. Brower, pers. commun.) and Caenorhabditis elegans20. The gene encoding human ILK has been localized to human chromosome 11p15.5–p15.4 (Ref. 16). Regional loss of heterozygosity (LOH) indicates that this part of chromosome 11 is strongly associated with tumorigenesis in a manner that might involve genomic imprinting17. Thus, it is possible that dysregulation of ILK function could be a consequence
Mammalian ILK in integrin and growth factor signalling
Two independent strategies have led to insight into the likely physiological role(s) of ILK. These are analysis of alteration in ILK kinase activity upon cell attachment to ECM substrates, and stimulation with growth factors; and gain or loss of function using overexpression by cDNA transfection or mutational analysis, respectively.
Evaluation of the effects of cell adhesion and growth-factor stimulation has shown that the kinase activity of ILK is under stringent control by these stimuli.
Concluding remarks
ILK is an evolutionarily conserved serine/threonine protein kinase containing ankyrin repeats and phosphoinositide phospholipid-binding motifs. ILK is capable of interacting directly with integrin β1, β2 and β3 subunits and might be involved in their phosphorylation. In C. elegans, ILK might function to promote the assembly of focal-adhesion-like muscle attachments, together with integrins and another ILK-interacting protein, PINCH. ILK also appears to be an important effector of integrin and
Note added in proof
It has recently been shown that PDK-1 can, under certain highly artificial and nonphysiological conditions, phosphorylate PKB on Ser473 (Ref. 38). This does not negate the ability of other kinases, such as ILK, also to phosphorylate Ser473 of PKB. In fact, ILK might be a more physiologically relevant PDK-2 as dominant–negative ILK inhibits this phosphorylation in intact cells9.
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