A critical role of the PINCH-integrin-linked kinase interaction in the regulation of cell shape change and migration.
The interaction of cells with extracellular matrix recruits multiple proteins to cell-matrix contact sites (e.g. focal and fibrillar adhesions), which connect the extracellular matrix to the actin cytoskeleton and regulate cell shape change, migration, and other cellular processes. We previously identified PINCH, an adaptor protein comprising primarily five LIM domains, as a binding protein for integrin-linked kinase (ILK). In this study, we show that PINCH co-localizes with ILK in both focal adhesions and fibrillar adhesions. Furthermore, we have investigated the molecular basis underlying the targeting of PINCH to the cell-matrix contact sites and the functional significance of the PINCH-ILK interaction. We have found that the N-terminal LIM1 domain, which mediates the ILK binding, is required for the targeting of PINCH to the cell-matrix contact sites. The C-terminal LIM domains, although not absolutely required, play an important regulatory role in the localization of PINCH to cell-matrix contact sites. Inhibition of the PINCH-ILK interaction, either by overexpression of a PINCH N-terminal fragment containing the ILK-binding LIM1 domain or by overexpression of an ILK N-terminal fragment containing the PINCH-binding ankyrin domain, retarded cell spreading, and reduced cell motility. These results suggest that PINCH, through its interaction with ILK, is crucially involved in the regulation of cell shape change and motility.
Zhang
Yongjun
Y
Department of Pathology, University of Pittsburgh, Pittsburgh, Pennsylvania 15261, USA.
Guo
Lida
L
Chen
Ka
K
Wu
Chuanyue
C
D001665:Binding Sites; D002448:Cell Adhesion; D002465:Cell Movement; D048429:Cell Size; D004268:DNA-Binding Proteins / Q000032:analysis / Q000737:chemistry / Q000502:physiology*; D017346:Protein Serine-Threonine Kinases / Q000032:analysis / Q000502:physiology*; D000099200:Scaffold Protein ILK
D004268:DNA-Binding Proteins; D017346:Protein Serine-Threonine Kinases; D000099200:Scaffold Protein ILK