Published online 5 March 2001. doi:10.1083/jcb.152.5.1007
© The Rockefeller University Press,
0021-9525/2001//1007 $5.00
The Journal of Cell Biology, Volume 152, Number 5,
, 2001 1007-1018
Drosophila Integrin-Linked Kinase Is Required at Sites of Integrin Adhesion to Link the Cytoskeleton to the Plasma Membrane
Christos G. Zervasa,
Stephen L. Gregorya, and
Nicholas H. Browna
a Wellcome/CRC Institute and Department of Anatomy, University of Cambridge, Cambridge CB2 1QR, United Kingdom
Wellcome/CRC Institute, Tennis Court Rd., Cambridge, CB2 1QR, UK.44-1223-33408944-1223-334128
nb117{at}mole.bio.cam.ac.uk
Integrin-linked kinase (ILK) was identified by its interaction with the cytoplasmic tail of human β1 integrin and previous data suggest that ILK is a component of diverse signaling pathways, including integrin, Wnt, and protein kinase B. Here we show that the absence of ILK function in Drosophila causes defects similar to loss of integrin adhesion, but not similar to loss of these signaling pathways. ILK mutations cause embryonic lethality and defects in muscle attachment, and clones of cells lacking ILK in the adult wing fail to adhere, forming wing blisters. Consistent with this, an ILK–green fluorescent protein fusion protein colocalizes with the position-specific integrins at sites of integrin function: muscle attachment sites and the basal junctions of the wing epithelium. Surprisingly, mutations in the kinase domain shown to inactivate the kinase activity of human ILK do not show any phenotype in Drosophila, suggesting a kinase-independent function for ILK. The muscle detachment in ILK mutants is associated with detachment of the actin filaments from the muscle ends, unlike integrin mutants, in which the primary defect is detachment of the plasma membrane from the extracellular matrix. Our data suggest that ILK is a component of the structure linking the cytoskeleton and the plasma membrane at sites of integrin-mediated adhesion.
Key Words: integrins cell adhesion cytoskeleton kinase Drosophila
© 2001 The Rockefeller University Press
Abbreviations used in this paper: ECM, extracellular matrix; GFP, green fluorescent protein; ILK, integrin-linked kinase; PS, position specific.

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-
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-
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-
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-
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[Abstract]
[Full Text]
-
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[Full Text]
-
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[Abstract]
[Full Text]
-
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[Full Text]
-
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118: 2913-2921
[Abstract]
[Full Text]
-
Hooper, S. L., Thuma, J. B.
(2005). Invertebrate Muscles: Muscle Specific Genes and Proteins. Physiol. Rev.
85: 1001-1060
[Abstract]
[Full Text]
-
Liang, X., Zhou, Q., Li, X., Sun, Y., Lu, M., Dalton, N., Ross, J. Jr., Chen, J.
(2005). PINCH1 Plays an Essential Role in Early Murine Embryonic Development but Is Dispensable in Ventricular Cardiomyocytes. Mol. Cell. Biol.
25: 3056-3062
[Abstract]
[Full Text]
-
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10: 369-379
[Abstract]
[Full Text]
-
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(2005). Papillote and Piopio: Drosophila ZP-domain proteins required for cell adhesion to the apical extracellular matrix and microtubule organization. J. Cell Sci.
118: 633-642
[Abstract]
[Full Text]
-
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(2004). The Integrin-linked Kinase Regulates Cell Morphology and Motility in a Rho-associated Kinase-dependent Manner. J. Biol. Chem.
279: 54131-54139
[Abstract]
[Full Text]
-
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(2004). Focal adhesion kinase is not required for integrin function or viability in Drosophila. Development
131: 5795-5805
[Abstract]
[Full Text]
-
Brown, M. C., Turner, C. E.
(2004). Paxillin: Adapting to Change. Physiol. Rev.
84: 1315-1339
[Abstract]
[Full Text]
-
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(2004). Identification of a PKB/Akt Hydrophobic Motif Ser-473 Kinase as DNA-dependent Protein Kinase. J. Biol. Chem.
279: 41189-41196
[Abstract]
[Full Text]
-
Clarke, D. M., Brown, M. C., LaLonde, D. P., Turner, C. E.
(2004). Phosphorylation of actopaxin regulates cell spreading and migration. JCB
166: 901-912
[Abstract]
[Full Text]
-
Vouret-Craviari, V., Boulter, E., Grall, D., Matthews, C., Van Obberghen-Schilling, E.
(2004). ILK is required for the assembly of matrix-forming adhesions and capillary morphogenesis in endothelial cells. J. Cell Sci.
117: 4559-4569
[Abstract]
[Full Text]
-
Cordes, N.
(2004). Overexpression of Hyperactive Integrin-Linked Kinase Leads to Increased Cellular Radiosensitivity. Cancer Res.
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[Abstract]
[Full Text]
-
Cox, E. A., Hardin, J.
(2004). Sticky worms: adhesion complexes in C. elegans. J. Cell Sci.
117: 1885-1897
[Abstract]
[Full Text]
-
Ahmed, N., Oliva, K., Rice, G. E, Quinn, M. A
(2004). Cell-Free 59 kDa Immunoreactive Integrin-Linked Kinase: A Novel Marker for Ovarian Carcinoma. Clin. Cancer Res.
10: 2415-2420
[Abstract]
[Full Text]
-
Fukuda, T., Chen, K., Shi, X., Wu, C.
(2003). PINCH-1 Is an Obligate Partner of Integrin-linked Kinase (ILK) Functioning in Cell Shape Modulation, Motility, and Survival. J. Biol. Chem.
278: 51324-51333
[Abstract]
[Full Text]
-
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(2003). Integration of Cell Attachment, Cytoskeletal Localization, and Signaling by Integrin-linked Kinase (ILK), CH-ILKBP, and the Tumor Suppressor PTEN. Mol. Biol. Cell
14: 4813-4825
[Abstract]
[Full Text]
-
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(2003). Integrin-linked kinase is required for laminin-2-induced oligodendrocyte cell spreading and CNS myelination. JCB
163: 397-408
[Abstract]
[Full Text]
-
Lee, S. B., Cho, K. S., Kim, E., Chung, J.
(2003). blistery encodes Drosophila tensin protein and interacts with integrin and the JNK signaling pathway during wing development. Development
130: 4001-4010
[Abstract]
[Full Text]
-
Terpstra, L., Prud'homme, J., Arabian, A., Takeda, S., Karsenty, G., Dedhar, S., St-Arnaud, R.
(2003). Reduced chondrocyte proliferation and chondrodysplasia in mice lacking the integrin-linked kinase in chondrocytes. JCB
162: 139-148
[Abstract]
[Full Text]
-
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(2003). Analysis of PINCH function in Drosophila demonstrates its requirement in integrin-dependent cellular processes. Development
130: 2611-2621
[Abstract]
[Full Text]
-
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(2003). Conditional Knock-out of Integrin-linked Kinase Demonstrates an Essential Role in Protein Kinase B/Akt Activation. J. Biol. Chem.
278: 22374-22378
[Abstract]
[Full Text]
-
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(2003). Integrin-linked kinase (ILK) is required for polarizing the epiblast, cell adhesion, and controlling actin accumulation. Genes Dev.
17: 926-940
[Abstract]
[Full Text]
-
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(2003). Ca2+-dependent Localization of Integrin-linked Kinase to Cell Junctions in Differentiating Keratinocytes. J. Biol. Chem.
278: 11528-11535
[Abstract]
[Full Text]
-
Zhang, Y., Chen, K., Tu, Y., Velyvis, A., Yang, Y., Qin, J., Wu, C.
(2003). Assembly of the PINCH-ILK-CH-ILKBP complex precedes and is essential for localization of each component to cell-matrix adhesion sites. J. Cell Sci.
115: 4777-4786
[Abstract]
[Full Text]
-
Roberts, M. S., Woods, A. J., Shaw, P. E., Norman, J. C.
(2003). ERK1 Associates with alpha vbeta 3 Integrin and Regulates Cell Spreading on Vitronectin. J. Biol. Chem.
278: 1975-1985
[Abstract]
[Full Text]
-
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277: 38328-38338
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[Full Text]
-
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277: 34359-34366
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-
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(2002). c-erbB2-induced Disruption of Matrix Adhesion and Morphogenesis Reveals a Novel Role for Protein Kinase B as a Negative Regulator of alpha 2beta 1 Integrin Function. Mol. Biol. Cell
13: 2894-2908
[Abstract]
[Full Text]
-
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(2002). Integrin-linked Kinase Regulates Inducible Nitric Oxide Synthase and Cyclooxygenase-2 Expression in an NF-kappa B-dependent Manner. J. Biol. Chem.
277: 3109-3116
[Abstract]
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-
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(2001). Integrin-linked kinase (ILK) and its interactors: a new paradigm for the coupling of extracellular matrix to actin cytoskeleton and signaling complexes. JCB
155: 505-510
[Abstract]
[Full Text]
-
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(2001). The Distribution and Regulation of Integrin-Linked Kinase in Normal and Diabetic Kidneys. Am. J. Pathol.
159: 1735-1742
[Abstract]
[Full Text]
-
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(2001). A New Focal Adhesion Protein That Interacts with Integrin-Linked Kinase and Regulates Cell Adhesion and Spreading. JCB
153: 585-598
[Abstract]
[Full Text]
-
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(2002). A Critical Role of the PINCH-Integrin-linked Kinase Interaction in the Regulation of Cell Shape Change and Migration. J. Biol. Chem.
277: 318-326
[Abstract]
[Full Text]
-
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(2002). Molecular Dissection of Actopaxin-Integrin-linked Kinase-Paxillin Interactions and Their Role in Subcellular Localization. J. Biol. Chem.
277: 1568-1575
[Abstract]
[Full Text]