This Article Full Text Full Text (PDF) Alert me when this article is cited Alert me if a correction is posted Citation Map Services Email this article to a friend Similar articles in this journal Similar articles in PubMed Alert me to new issues of the journal Download to citation manager Request Permissions Citing Articles Citing Articles via HighWire Citing Articles via Google Scholar Google Scholar Articles by Hannigan, G. E. Articles by Dedhar, S. Search for Related Content PubMed PubMed Citation Articles by Hannigan, G. E. Articles by Dedhar, S. Pubmed/NCBI databases Substance via MeSH Medline Plus Health Information Cardiomyopathy Related Collections Contractile function Remodeling Cell signalling/signal transduction Genetically altered mice Heart failure - basic studies Hypertrophy Myocardial cardiomyopathy disease

(Circulation Research. 2007;100:1408.)
© 2007 American Heart Association, Inc.

MiniReview

Integrin-Linked Kinase at the Heart of Cardiac Contractility, Repair, and Disease

Gregory E. Hannigan, John G. Coles, Shoukat Dedhar

From the Department of Laboratory Medicine & Pathobiology, University of Toronto, and Cell Biology Program (G.E.H.), The Hospital for Sick Children MaRS Centre, Ontario; Department of Surgery, University of Toronto, and Physiology & Experimental Medicine Program (J.G.C.), Hospital for Sick Children Research Institute, Ontario; and Department of Biochemistry and Molecular Biology (S.D.), University of British Columbia and British Columbia Cancer Research Centre, Vancouver, Canada.

Correspondence to Dr G. Hannigan, The Hospital for Sick Children, MaRS Centre, Toronto Medical Discovery Tower, Room 12-308, 101 College St, Toronto, ON M5G 1L7, Canada.

Abstract

Recent advances in cardiac physiology identify the integrin-linked kinase (ILK) as an essential molecule regulating cardiac growth, contractility, and repair. A key transducer of biochemical signals initiated at the plasma membrane by cell–matrix interactions, ILK now emerges as a crucial player in mechanotransduction by integrins. Animal models have been particularly instructive in dissecting the cardiac functions of ILK and its associated proteins, such as parvins and PINCH, and have clearly established ILK as a major contributor to cardiac health. ILK gene knockouts in mice, flies, and worms result in early embryonic lethality because of cell adhesion defects and cytoskeletal disorganization. Although widely distributed in mammalian tissues, ILK expression is highest in the heart, and cardiac-specific ablation of ILK causes cardiomyopathy and sudden death in mice. ILK protein complexes are found in the sarcomere, which is the basic contractile unit of myocytes. A natural inactivating mutation in the kinase domain of ILK disrupts ILK protein interactions in the sarcomere, causing a contractile defect in the zebrafish heart. The relatively subtle phenotype of mutant ILK hearts, compared with ILK-ablated hearts, suggests multiple cardiac ILK functions. Cardiac-specific expression of ILK in transgenic mice induces a hypertrophic program, pointing to ILK as a proximal regulator of multiple hypertrophic signal transduction pathways. ILK protein interactions may also be important in mediating postinfarct cell migration and myocardial repair.

Key Words: integrin-linked kinase • cardiac hypertrophy • cardiomyopathy

This article has been cited by other articles:

				K. R. Legate and R. Fassler Mechanisms that regulate adaptor binding to {beta}-integrin cytoplasmic tails J. Cell Sci., January 15, 2009; 122(2): 187 - 198. [Abstract] [Full Text] [PDF]

				P. C. McDonald, A. B. Fielding, and S. Dedhar Integrin-linked kinase - essential roles in physiology and cancer biology J. Cell Sci., October 1, 2008; 121(19): 3121 - 3132. [Abstract] [Full Text] [PDF]

				C. X. Fang, F. Dong, D. P. Thomas, H. Ma, L. He, and J. Ren Hypertrophic cardiomyopathy in high-fat diet-induced obesity: role of suppression of forkhead transcription factor and atrophy gene transcription Am J Physiol Heart Circ Physiol, September 1, 2008; 295(3): H1206 - H1215. [Abstract] [Full Text] [PDF]

				S. M. Dallabrida, N. S. Ismail, E. A. Pravda, E. M. Parodi, R. Dickie, E. M. Durand, J. Lai, F. Cassiola, R. A. Rogers, and M. A. Rupnick Integrin binding angiopoietin-1 monomers reduce cardiac hypertrophy FASEB J, August 1, 2008; 22(8): 3010 - 3023. [Abstract] [Full Text] [PDF]

				Z.-F. Lai, Y.-Z. Chen, L.-P. Feng, X.-M. Meng, J.-F. Ding, L.-Y. Wang, J. Ye, P. Li, X.-S. Cheng, Y. Kitamoto, et al. Overexpression of TNNI3K, a cardiac-specific MAP kinase, promotes P19CL6-derived cardiac myogenesis and prevents myocardial infarction-induced injury Am J Physiol Heart Circ Physiol, August 1, 2008; 295(2): H708 - H716. [Abstract] [Full Text] [PDF]

				M. Dittrich, I. Birschmann, S. Mietner, A. Sickmann, U. Walter, and T. Dandekar Platelet Protein Interactions: Map, Signaling Components, and Phosphorylation Groundstate Arterioscler. Thromb. Vasc. Biol., July 1, 2008; 28(7): 1326 - 1331. [Abstract] [Full Text] [PDF]

				B. Ho, G. Hou, J. G. Pickering, G. Hannigan, B. L. Langille, and M. P. Bendeck Integrin-Linked Kinase in the Vascular Smooth Muscle Cell Response to Injury Am. J. Pathol., July 1, 2008; 173(1): 278 - 288. [Abstract] [Full Text] [PDF]

				M. Philippova, D. Ivanov, M. B. Joshi, E. Kyriakakis, K. Rupp, T. Afonyushkin, V. Bochkov, P. Erne, and T. J. Resink Identification of Proteins Associating with Glycosylphosphatidylinositol- Anchored T-Cadherin on the Surface of Vascular Endothelial Cells: Role for Grp78/BiP in T-Cadherin-Dependent Cell Survival Mol. Cell. Biol., June 15, 2008; 28(12): 4004 - 4017. [Abstract] [Full Text] [PDF]

				J. J. Dowling, E. Gibbs, M. Russell, D. Goldman, J. Minarcik, J. A. Golden, and E. L. Feldman Kindlin-2 Is an Essential Component of Intercalated Discs and Is Required for Vertebrate Cardiac Structure and Function Circ. Res., February 29, 2008; 102(4): 423 - 431. [Abstract] [Full Text] [PDF]

				M. Moustafa-Bayoumi, M. A. Alhaj, O. El-Sayed, S. Wisel, M. A. Chotani, Z. A. Abouelnaga, M. D. H. Hassona, K. Rigatto, M. Morris, G. Nuovo, et al. Vascular Hypertrophy and Hypertension Caused by Transgenic Overexpression of Profilin 1 J. Biol. Chem., December 28, 2007; 282(52): 37632 - 37639. [Abstract] [Full Text] [PDF]