ILK
Domain
The kinase domain is likely to have lost catalytic activity but retains ATP-binding activity (PubMed:20005845, PubMed:21524996). ATP structurally stabilizes the kinase domain and promotes stability of binding to PARVA as well as focal adhesion stability (PubMed:35259013).
The PH-like region is not required for assembly of the IPP complex or for localization of ILK to focal adhesions.
Function
Scaffold protein which mediates protein-protein interactions during a range of cellular events including focal adhesion assembly, cell adhesion and cell migration (PubMed:17420447, PubMed:20005845, PubMed:30367047, PubMed:32528174). Regulates integrin-mediated signal transduction by contributing to inside-out integrin activation (By similarity). Recruits PARVA and LIMS1/PITCH to form the heterotrimeric IPP (ILK-PINCH-PARVIN) complex which binds to F-actin via the C-terminal tail of LIMS1 and the N-terminal region of PARVA, promoting F-actin filament bundling, a process required to generate force for actin cytoskeleton reorganization and subsequent dynamic cell adhesion events such as cell spreading and migration (PubMed:30367047). Binding to PARVA promotes effective assembly of ILK into focal adhesions while PARVA-bound ILK can simultaneously engage integrin-beta cytoplasmic tails to mediate cell adhesion (PubMed:20005845). Plays a role with PARVG in promoting the cell adhesion and spreading of leukocytes (PubMed:16517730). Acts as an upstream effector of both AKT1/PKB and GSK3 (PubMed:9736715). Mediates trafficking of caveolae to the cell surface in an ITGB1-dependent manner by promoting the recruitment of IQGAP1 to the cell cortex which cooperates with its effector DIAPH1 to locally stabilize microtubules and allow stable insertion of caveolae into the plasma membrane (By similarity). Required for the maintenance of mitotic spindle integrity by promoting phosphorylation of TACC3 by AURKA (PubMed:18283114). Associates with chromatin and may act as a negative regulator of transcription when located in the nucleus (PubMed:17420447).
Post-translational modifications
Phosphorylation by PAK1 modulates ILK subcellular location by promoting its nuclear export.
Sequence Similarities
Belongs to the protein kinase superfamily. TKL Ser/Thr protein kinase family.
Tissue Specificity
Highly expressed in heart followed by skeletal muscle, pancreas and kidney. Weakly expressed in placenta, lung and liver.
Cellular localization
- Cell junction
- Focal adhesion
- Cell membrane
- Peripheral membrane protein
- Cytoplasmic side
- Cell projection
- Lamellipodium
- Cytoplasm
- Myofibril
- Sarcomere
- Cytoplasm
- Nucleus
- Cytoplasm
- Cytoskeleton
- Microtubule organizing center
- Centrosome
- Cytoplasm
- Cell cortex
Alternative names
ILK1, ILK2, ILK, Scaffold protein ILK, ILK-1, ILK-2, Inactive integrin-linked kinase, p59ILK