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Regulation of cell‐matrix adhesion dynamics and Rac‐1 by integrin linked kinase
Author(s) -
Boulter Etienne,
Grall Dominique,
Cagnol Sébastien,
Van Obberghen-Schilling Ellen
Publication year - 2006
Publication title -
the faseb journal
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.709
H-Index - 277
eISSN - 1530-6860
pISSN - 0892-6638
DOI - 10.1096/fj.05-4579fje
Subject(s) - integrin linked kinase , microbiology and biotechnology , integrin , fibronectin , focal adhesion , chemistry , cdc42 , extracellular matrix , cell adhesion , kinase , signal transduction , biology , cell , protein kinase a , biochemistry , cyclin dependent kinase 2
Extracellular matrix (ECM) receptors of the integrin family initiate changes in cell shape and motility by recruiting signaling components that coordinate these events. Integrin‐linked kinase (ILK) is one such partner of β1 integrins that participates in dynamic rearrangement of cell‐matrix adhesions and cell spreading by mechanisms that are not well understood. To further elucidate the role of ILK in these events, we engineered a chimeric molecule comprising ILK fused to a membrane‐targeted green fluorescent protein (ILK‐GFP‐F). ILK‐GFP‐F is highly enriched in cell‐matrix adhesions, and its expression in fibroblasts leads to an accumulation of focal adhesions (2–5 µm) and elongated adhesions (>5 µm). ILK‐GFP‐F enhances cell spreading on fibronectin and induces a constitutive increase in the levels of GTP‐bound Rac‐1. Conversely, ILK knock‐down by siRNA transfection decreases active Rac‐1. Endogenous ILK was found to associate with PKL (paxillin kinase linker) and the Rac/Cdc42 guanine nucleotide exchange factor βPIX. Further, expression of a dominant negative βPIX mutant reversed the increase in active Rac‐1 levels of ILK‐GFP‐F‐expressing cells, thus placing βPIX in the pathway leading from ILK to Rac‐1 activation. However, expression of constitutively active Rac only partially restores the spreading defects of ILK‐depleted cells, suggesting that an additional ILK‐dependent signal is required for cell spreading.—Boulter, E., Grall, D., Cagnol, S., and Van Obberghen‐Schilling, E. Regulation of cell‐matrix adhesion dynamics and Rac‐1 by integrin linked kinase. FASEB J. 20, E640‐E651 (2006)