The pseudokinase domain shows similarity to protein kinases but lacks crucial residues for catalytic activity. Integrin linked kinase (ILK) contains N-terminal ankyrin repeats, a Pleckstrin Homology (PH) domain, and a C-terminal pseudokinase domain. It is a component of the IPP (ILK/PINCH/Parvin) complex that couples beta integrins to the actin cytoskeleton, and plays important roles in cell adhesion, spreading, invasion, and migration []. ILK was initially thought to be an active kinase despite the lack of key conserved residues because of in vitro studies showing that it can phosphorylate certain protein substrates. However, in vivo experiments in Caenorhabditis elegans, Drosophila melanogaster, and mice (ILK-null and knock-in) proved that ILK is not an active kinase []. In addition to actin cytoskeleton regulation, ILK also influences the microtubule network and mitotic spindle orientation [, ]. The pseudokinase domain of ILK binds several adaptor proteins including the parvins and paxillin [, ].
In general, LIM domains coordinate one or more zinc atoms, and are named after the three proteins (LIN-11, Isl1 and MEC-3) in which they were first found. They consist of two zinc-binding motifs that resemble GATA-like Znf's, however the residues holding the zinc atom(s) are variable, involving Cys, His, Asp or Glu residues. LIM domain-containing proteins have diverse cellular roles such as regulators of gene expression, cyto-architecture, cell adhesion, cell motility, and signal transduction. LIM domain-containing proteins have been shown to be key molecules in a wide variety of human cancers [].LIMD2 binds directly to the kinase domain of integrin-linked kinase (ILK) near the active site and strongly activated ILK kinase activity. Its LIM-domain structure is highly related to LIM1 of PINCH1, a core component of the integrin-linked kinase-parvin-pinch complex [].
