Article ID | Journal | Published Year | Pages | File Type |
---|---|---|---|---|
10816397 | Cellular Signalling | 2005 | 10 Pages |
Abstract
Integrin linked kinase 1 (ILK1), a member of the serine/threonine kinases, has been shown to be crucial for the cell survival, differentiation, and Wnt signaling. Firstly, by using a confocal microscopy and a transfection approach, we obtained the evidence that ILK1 interacts physically with caveolin-1, a 22-kDa integral membrane protein, which is the principal structural and regulatory component of caveolae membranes. By ILK1 deletion mutant analysis, we characterized the caveolin-1-binding domain in the kinase domain of ILK1. In addition, we found that native ILK1 is associated with endogenous caveolin-1 in COS-1 cells. Secondly, transient transfection assays showed that a reduction in caveolin-1 binding leads to a substantial increase in the serine/threonine phosphorylation of ILK1. Thirdly, caveolin-1 and its scaffolding peptide (amino acids 82-101) functionally suppressed the auto-kinase activity of purified recombinant ILK1 protein. Fourthly, the association of ILK1 with caveolin-1 regulated its cytoplasmic retention; if it was not associated with caveolin-1, it was transported to the nucleus. Fifthly, we also noticed the putative nuclear localization sequences (nls) in ILK1 near the caveolin-1-binding domain. Thus, our data indicate that caveolin-1 regulates ILK1 auto-phosphorylation activity and its subcellular localization via a specific protein-protein interaction through blocking the exposure of its putative nls motif.
Related Topics
Life Sciences
Biochemistry, Genetics and Molecular Biology
Biochemistry
Authors
Jaesun Chun, Sunghee Hyun, Taegun Kwon, Eun Jeoung Lee, Soon-Kwang Hong, Sang Sun Kang,