REGULATION OF CELL-ADHESION AND ANCHORAGE-DEPENDENT GROWTH BY A NEW BETA(1)-INTEGRIN-LINKED PROTEIN-KINASE

THE interaction of cells with the extracellular matrix regulates cell shape, motility, growth, survival, differentiation and gene expression , through integrin-mediated signal transduction(1-3). We used a two-hy brid screen to isolate genes encoding proteins that interact with the beta(1)-integrin cytoplasmic domain. The most frequently isolated comp lementary DNA encoded a new, 59K serine/threonine protein kinase, cont aining four ankyrin-like repeats. We report here that this integrin-li nked kinase (ILK) phosphorylated a beta(1)-integrin cytoplasmic domain peptide in vitro and coimmunoprecipitated with beta(1) in lysates of mammalian cells. Endogenous ILK kinase activity was reduced in respons e to fibronectin. Overexpression of p59(ILK) disrupted epithelial cell architecture and inhibited adhesion to integrin substrates, while ind ucing anchorage-independent growth. We propose that ILK is a receptor- proximal protein kinase regulating integrin-mediated signal transducti on.