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. We used a two-hybrid screen to isolate genes encoding proteins that interact with the beta 1-integrin cytoplasmic domain. The most frequently isolated complementary DNA encoded a new, 59K serine/threonine protein kinase, containing four ankyrin-like repeats. We report here that this integrin-linked 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 response to fibronectin. Overexpression of p59ILK disrupted epithelial cell architecture and inhibited adhesion to integrin substrates, while inducing anchorage-independent growth. We propose that ILK is a receptor-proximal protein kinase regulating integrin-mediated signal transduction.
Cancer Biology Research Program, Sunnybrook Health Science Centre, University of Toronto, Ontario, Canada.
G E
GE
Hannigan
C
C
Leung-Hagesteijn
L
L
Fitz-Gibbon
M G
MG
Coppolino
G
G
Radeva
J
J
Filmus
J C
JC
Bell
S
S
Dedhar
D000595:Amino Acid Sequence; D000818:Animals; D000906:Antibodies / Q000276:immunology; D001483:Base Sequence; D002448:Cell Adhesion; D002455:Cell Division; D002460:Cell Line; D018076:DNA, Complementary; D005109:Extracellular Matrix / Q000378:metabolism; D005353:Fibronectins / Q000378:metabolism; D006801:Humans; D019012:Integrin beta1 / Q000378:metabolism*; D008969:Molecular Sequence Data; D004676:Myelin Basic Protein / Q000378:metabolism; D010766:Phosphorylation; D017346:Protein Serine-Threonine Kinases / Q000235:genetics / Q000276:immunology / Q000378:metabolism*; D051381:Rats; D011993:Recombinant Fusion Proteins / Q000235:genetics / Q000378:metabolism; D000099200:Scaffold Protein ILK
D000906:Antibodies; D018076:DNA, Complementary; D005353:Fibronectins; D019012:Integrin beta1; D004676:Myelin Basic Protein; D017346:Protein Serine-Threonine Kinases; D011993:Recombinant Fusion Proteins; D000099200:Scaffold Protein ILK