![[Feedback]](/icons/banner/feedbackACT.gif){kind=icon}
![[For Subscribers]](/icons/banner/subscriberACT.gif){kind=icon}
![[Archive]](/icons/banner/archiveACT.gif){kind=icon}
![[Search]](/icons/banner/searchACT.gif){kind=icon}
![[Contents]](/icons/banner/tocACT.gif){kind=icon}
|
|
|
|
|
||
Vol. 14, Issue 12, 4813-4825, December 2003
| ||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
* BC Cancer Agency, Jack Bell Research Centre, Vancouver, BC, V6H 3Z6, Canada;
Genetics Graduate Program, University of British Columbia, Vancouver, BC, Canada;
Department of Biochemistry and Molecular Biology, University of British Columbia, Vancouver, BC, Canada; and
Department of Pathology, University of Pittsburgh, Pittsburgh, Pennsylvania
Submitted May 15, 2003;
Revised July 31, 2003;
Accepted July 31, 2003
Monitoring Editor: Mark Ginsberg
Cell attachment and the assembly of cytoskeletal and signaling complexes downstream of integrins are intimately linked and coordinated. Although many intracellular proteins have been implicated in these processes, a new paradigm is emerging from biochemical and genetic studies that implicates integrin-linked kinase (ILK) and its interacting proteins, such as CH-ILKBP (
-parvin), paxillin, and PINCH in coupling integrins to the actin cytoskeleton and signaling complexes. Genetic studies in Drosophila, Caenorhabditis elegans, and mice point to an essential role of ILK as an adaptor protein in mediating integrin-dependent cell attachment and cytoskeletal organization. Here we demonstrate, using several different approaches, that inhibiting ILK kinase activity, or expression, results in the inhibition of cell attachment, cell migration, F-actin organization, and the specific cytoskeletal localization of CH-ILKBP and paxillin in human cells. We also demonstrate that the kinase activity of ILK is elevated in the cytoskeletal fraction and that the interaction of CH-ILKBP with ILK within the cytoskeleton stimulates ILK activity and downstream signaling to PKB/Akt and GSK-3. Interestingly, the interaction of CH-ILKBP with ILK is regulated by the Pi3 kinase pathway, because inhibition of Pi3 kinase activity by pharmacological inhibitors, or by the tumor suppressor PTEN, inhibits this interaction as well as cell attachment and signaling. These data demonstrate that the kinase and adaptor properties of ILK function together, in a Pi3 kinase–dependent manner, to regulate integrin-mediated cell attachment and signal transduction.
Corresponding author. E-mail address: sdedhar{at}interchange.ubc.ca.
This article has been cited by other articles:
|
|
 |
|
  J. A. Ardura, S. Rayego-Mateos, D. Ramila, M. Ruiz-Ortega, and P. Esbrit Parathyroid Hormone-Related Protein Promotes Epithelial-Mesenchymal Transition J. Am. Soc. Nephrol., February 1, 2010; 21(2): 237 - 248. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 Y. Wu, Y. Huang, B. P. Herring, and S. J. Gunst Integrin-linked kinase regulates smooth muscle differentiation marker gene expression in airway tissue Am J Physiol Lung Cell Mol Physiol, December 1, 2008; 295(6): L988 - L997. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 M. S. Weaver, G. Workman, and E. H. Sage The Copper Binding Domain of SPARC Mediates Cell Survival in Vitro via Interaction with Integrin {beta}1 and Activation of Integrin-linked Kinase J. Biol. Chem., August 15, 2008; 283(33): 22826 - 22837. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
Y.-B. Kim, S. Choi, M.-C. Choi, M.-A Oh, S.-A. Lee, M. Cho, K. Mizuno, S.-H. Kim, and J. W. Lee Cell Adhesion-dependent Cofilin Serine 3 Phosphorylation by the Integrin-linked Kinase{middle dot}c-Src Complex J. Biol. Chem., April 11, 2008; 283(15): 10089 - 10096. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
W. Zhang, Y. Wu, C. Wu, and S. J. Gunst Integrin-linked Kinase Regulates N-WASp-mediated Actin Polymerization and Tension Development in Tracheal Smooth Muscle J. Biol. Chem., November 23, 2007; 282(47): 34568 - 34580. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 R. P.C. Wong, P. Ng, S. Dedhar, and G. Li The role of integrin-linked kinase in melanoma cell migration, invasion, and tumor growth Mol. Cancer Ther., June 1, 2007; 6(6): 1692 - 1700. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 D. Flugel, A. Gorlach, C. Michiels, and T. Kietzmann Glycogen Synthase Kinase 3 Phosphorylates Hypoxia-Inducible Factor 1{alpha} and Mediates Its Destabilization in a VHL-Independent Manner Mol. Cell. Biol., May 1, 2007; 27(9): 3253 - 3265. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 N. Said, I. Najwer, and K. Motamed Secreted Protein Acidic and Rich in Cysteine (SPARC) Inhibits Integrin-Mediated Adhesion and Growth Factor-Dependent Survival Signaling in Ovarian Cancer Am. J. Pathol., March 1, 2007; 170(3): 1054 - 1063. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 Y.-B. Kim, S.-Y. Lee, S.-K. Ye, and J. W. Lee Epigenetic regulation of integrin-linked kinase expression depending on adhesion of gastric carcinoma cells Am J Physiol Cell Physiol, February 1, 2007; 292(2): C857 - C866. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
S. V. Dandapani, H. Sugimoto, B. D. Matthews, R. J. Kolb, S. Sinha, R. E. Gerszten, J. Zhou, D. E. Ingber, R. Kalluri, and M. R. Pollak {alpha}-Actinin-4 Is Required for Normal Podocyte Adhesion J. Biol. Chem., January 5, 2007; 282(1): 467 - 477. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 D. Srivastava and S. Yu Stretching to meet needs: integrin-linked kinase and the cardiac pump Genes & Dev., September 1, 2006; 20(17): 2327 - 2331. [Full Text] [PDF]
|
|
|
|
|
|
G. Bendig, M. Grimmler, I. G. Huttner, G. Wessels, T. Dahme, S. Just, N. Trano, H. A. Katus, M. C. Fishman, and W. Rottbauer Integrin-linked kinase, a novel component of the cardiac mechanical stretch sensor, controls contractility in the zebrafish heart Genes & Dev., September 1, 2006; 20(17): 2361 - 2372. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
M. S. Shafiei and D. C. Rockey The Role of Integrin-linked Kinase in Liver Wound Healing J. Biol. Chem., August 25, 2006; 281(34): 24863 - 24872. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 M. Esfandiarei, A. Suarez, A. Amaral, X. Si, M. Rahmani, S. Dedhar, and B. M. McManus Novel Role for Integrin-Linked Kinase in Modulation of Coxsackievirus B3 Replication and Virus-Induced Cardiomyocyte Injury Circ. Res., August 18, 2006; 99(4): 354 - 361. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
C. El-Aouni, N. Herbach, S. M. Blattner, A. Henger, M. P. Rastaldi, G. Jarad, J. H. Miner, M. J. Moeller, R. St-Arnaud, S. Dedhar, et al. Podocyte-Specific Deletion of Integrin-Linked Kinase Results in Severe Glomerular Basement Membrane Alterations and Progressive Glomerulosclerosis J. Am. Soc. Nephrol., May 1, 2006; 17(5): 1334 - 1344. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 R. Yoshimi, S. Yamaji, A. Suzuki, W. Mishima, M. Okamura, T. Obana, C. Matsuda, Y. Miwa, S. Ohno, and Y. Ishigatsubo The {gamma}-Parvin-Integrin-Linked Kinase Complex Is Critically Involved in Leukocyte-Substrate Interaction J. Immunol., March 15, 2006; 176(6): 3611 - 3624. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 J. Mills, A. Niewmierzycka, A. Oloumi, B. Rico, R. St-Arnaud, I. R. Mackenzie, N. M. Mawji, J. Wilson, L. F. Reichardt, and S. Dedhar Critical Role of Integrin-Linked Kinase in Granule Cell Precursor Proliferation and Cerebellar Development J. Neurosci., January 18, 2006; 26(3): 830 - 840. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 B. Heit, P. Colarusso, and P. Kubes Fundamentally different roles for LFA-1, Mac-1 and {alpha}4-integrin in neutrophil chemotaxis J. Cell Sci., November 15, 2005; 118(22): 5205 - 5220. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
R. S. Nho, H. Xia, J. Kahm, J. Kleidon, D. Diebold, and C. A. Henke Role of Integrin-linked Kinase in Regulating Phosphorylation of Akt and Fibroblast Survival in Type I Collagen Matrices through a {beta}1 Integrin Viability Signaling Pathway J. Biol. Chem., July 15, 2005; 280(28): 26630 - 26639. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 E. D. Emberley, Y. Niu, L. Curtis, S. Troup, S. K. Mandal, J. N. Myers, S. B. Gibson, L. C. Murphy, and P. H. Watson The S100A7-c-Jun Activation Domain Binding Protein 1 Pathway Enhances Prosurvival Pathways in Breast Cancer Cancer Res., July 1, 2005; 65(13): 5696 - 5702. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 R. L. Juliano, V. R. Dixit, H. Kang, T. Y. Kim, Y. Miyamoto, and D. Xu Epigenetic manipulation of gene expression: a toolkit for cell biologists J. Cell Biol., June 20, 2005; 169(6): 847 - 857. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
D. P. LaLonde, M. C. Brown, B. P. Bouverat, and C. E. Turner Actopaxin Interacts with TESK1 to Regulate Cell Spreading on Fibronectin J. Biol. Chem., June 3, 2005; 280(22): 21680 - 21688. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
W. A. K. M. Khyrul, D. P. LaLonde, M. C. Brown, H. Levinson, and C. E. Turner The Integrin-linked Kinase Regulates Cell Morphology and Motility in a Rho-associated Kinase-dependent Manner J. Biol. Chem., December 24, 2004; 279(52): 54131 - 54139. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
H. M. Bill, B. Knudsen, S. L. Moores, S. K. Muthuswamy, V. R. Rao, J. S. Brugge, and C. K. Miranti Epidermal Growth Factor Receptor-Dependent Regulation of Integrin-Mediated Signaling and Cell Cycle Entry in Epithelial Cells Mol. Cell. Biol., October 1, 2004; 24(19): 8586 - 8599. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 M. C. Brown and C. E. Turner Paxillin: Adapting to Change Physiol Rev, October 1, 2004; 84(4): 1315 - 1339. [Abstract] [Full Text] [PDF]
|
|
