ILK, PINCH and parvin: the tIPP of integrin signalling

Key Points Adhesion of cells to the extracellular matrix (ECM) regulates processes that are related to cell survival, growth, differentiation, migration, polarity and proliferation. The main cell-surface receptors for ECM proteins are the integrins. Integrin-linked kinase (ILK), PINCH and parvin form a ternary complex (the IPP complex) that binds to ECM-ligated integrins. This complex regulates signalling pathways and connects the ECM with the actin cytoskeleton. Numerous isoforms of PINCH and parvin coexist to allow for the formation of different IPP complexes. Differential binding partners for PINCH and parvin isoforms might impart distinct functions to each complex. ILK has been identified as a Ser/Thr protein kinase in vitro . In vivo confirmation of kinase activity has proven difficult because mutations in ILK disrupt the assembly and function of the IPP complex. Genetic deletion of ILK, PINCH and parvin isoforms reveals common functions that are related to cell adhesion, but subtle differences in knockout phenotypes indicate separable functions outside of focal adhesions. The ternary complex of integrin-linked kinase (ILK), PINCH and parvin functions as a signalling platform for integrins by interfacing with the actin cytoskeleton and many diverse signalling pathways. All these proteins have synergistic functions at focal adhesions, but recent work has indicated that these proteins might also have separate roles within a cell. They function as regulators of gene transcription or cell–cell adhesion.