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doi: 10.1242/10.1242/jcs.00166

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Assembly of the PINCH-ILK-CH-ILKBP complex precedes and is essential for localization of each component to cell-matrix adhesion sites

¹ Department of Pathology, University of Pittsburgh, Pittsburgh, PA 15261, USA
² Structural Biology Program, Lerner Research Institute, The Cleveland Clinic Foundation, Cleveland, OH 44195, USA

^* Author for correspondence (e-mail: carywu{at}pitt.edu)

Accepted 11 September 2002

PINCH, integrin-linked kinase (ILK) and calponin homology-containing ILK-binding protein (CH-ILKBP) form a ternary complex that plays crucial roles at cell-extracellular matrix adhesion sites. To understand the mechanism underlying the complex formation and recruitment to cell-adhesion sites we have undertaken a combined structural, mutational and cell biological analysis. Three-dimensional structure-based point mutations identified specific PINCH and ILK sites that mediate the complex formation. Analyses of the binding defective point mutants revealed that the assembly of the PINCH-ILK-CH-ILKBP complex is essential for their localization to cell-extracellular matrix adhesion sites. The formation of the PINCH-ILK-CH-ILKBP complex precedes integrin-mediated cell adhesion and spreading. Furthermore, inhibition of protein kinase C, but not that of actin polymerization, inhibited the PINCH-ILK-CH-ILKBP complex formation, suggesting that the PINCH-ILK-CH-ILKBP complex likely serves as a downstream effector of protein kinase C in the cellular control of focal adhesion assembly. Finally, we provide evidence that the formation of the PINCH-ILK-CH-ILKBP complex, while necessary, is not sufficient for ILK localization to cell-extracellular matrix adhesion sites. These results provide new insights into the molecular mechanism underlying the assembly and regulation of cell-matrix adhesion structures.

Key words: Integrin-linked kinase, PINCH, CH-ILKBP, Focal adhesions, Protein kinase C

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