scholarly journals Beyond focal adhesions: Integrin linked kinase associates with tubulin and regulates mitotic spindle organization

Cell Cycle ◽  
2008 ◽  
Vol 7 (13) ◽  
pp. 1899-1906 ◽  
Author(s):  
Andrew B. Fielding ◽  
Iveta Dobreva ◽  
Shoukat Dedhar
Keyword(s):  
Mitotic Spindle ◽  
Focal Adhesions ◽  
Integrin Linked Kinase

scholarly journals Integrin-linked kinase localizes to the centrosome and regulates mitotic spindle organization

2008 ◽  
Vol 180 (4) ◽  
pp. 681-689 ◽  
Author(s):  
Andrew B. Fielding ◽  
Iveta Dobreva ◽  
Paul C. McDonald ◽  
Leonard J. Foster ◽  
Shoukat Dedhar
Keyword(s):  
Mitotic Spindle ◽  
Protein Complexes ◽  
Focal Adhesions ◽  
Spindle Pole ◽  
Serine Threonine Kinase ◽  
Centrosomal Protein ◽  
Threonine Kinase ◽  
Dna Segregation ◽  
Integrin Linked Kinase ◽  
Mitotic Spindle Assembly

Integrin-linked kinase (ILK) is a serine-threonine kinase and scaffold protein with well defined roles in focal adhesions in integrin-mediated cell adhesion, spreading, migration, and signaling. Using mass spectrometry–based proteomic approaches, we identify centrosomal and mitotic spindle proteins as interactors of ILK. α- and β-tubulin, ch-TOG (XMAP215), and RUVBL1 associate with ILK and colocalize with it to mitotic centrosomes. Inhibition of ILK activity or expression induces profound apoptosis-independent defects in the organization of the mitotic spindle and DNA segregation. ILK fails to localize to the centrosomes of abnormal spindles in RUVBL1-depleted cells. Additionally, depletion of ILK expression or inhibition of its activity inhibits Aurora A–TACC3/ch-TOG interactions, which are essential for spindle pole organization and mitosis. These data demonstrate a critical and unexpected function for ILK in the organization of centrosomal protein complexes during mitotic spindle assembly and DNA segregation.

Integrin-linked kinase is localized to cell-matrix focal adhesions but not cell-cell adhesion sites and the focal adhesion localization of integrin-linked kinase is regulated by the PINCH-binding ANK repeats

1999 ◽  
Vol 112 (24) ◽  
pp. 4589-4599 ◽  
Author(s):  
F. Li ◽  
Y. Zhang ◽  
C. Wu
Keyword(s):  
Focal Adhesion ◽  
Critical Role ◽  
Focal Adhesions ◽  
Subcellular Compartment ◽  
Cell Matrix ◽  
Integrin Binding Site ◽  
Integrin Linked Kinase ◽  
Cell Cell

Integrin-linked kinase (ILK) is a ubiquitously expressed protein serine/threonine kinase that has been implicated in integrin-, growth factor- and Wnt-signaling pathways. In this study, we show that ILK is a constituent of cell-matrix focal adhesions. ILK was recruited to focal adhesions in all types of cells examined upon adhesion to a variety of extracellular matrix proteins. By contrast, ILK was absent in E-cadherin-mediated cell-cell adherens junctions. In previous studies, we have identified PINCH, a protein consisting of five LIM domains, as an ILK binding protein. We demonstrate in this study that the ILK-PINCH interaction requires the N-terminal-most ANK repeat (ANK1) of ILK and one (the C-terminal) of the two zinc-binding modules within the LIM1 domain of PINCH. The ILK ANK repeats domain, which is capable of interacting with PINCH in vitro, could also form a complex with PINCH in vivo. However, the efficiency of the complex formation or the stability of the complex was markedly reduced in the absence of the C-terminal domain of ILK. The PINCH binding defective ANK1 deletion ILK mutant, unlike the wild-type ILK, was unable to localize and cluster in focal adhesions, suggesting that the interaction with PINCH is necessary for focal adhesion localization and clustering of ILK. The N-terminal ANK repeats domain, however, is not sufficient for mediating focal adhesion localization of ILK, as an ILK mutant containing the ANK repeats domain but lacking the C-terminal integrin binding site failed to localize in focal adhesions. These results suggest that focal adhesions are a major subcellular compartment where ILK functions in intracellular signal transduction, and provide important evidence for a critical role of PINCH and integrins in regulating ILK cellular function.

Phosphorylated SHIP2 on Y1135 localizes at focal adhesions and at the mitotic spindle in cancer cell lines

2014 ◽  
Vol 26 (6) ◽  
pp. 1193-1203 ◽  
Author(s):  
Laurence Deneubourg ◽  
William's Elong Edimo ◽  
Colette Moreau ◽  
Jean-Marie Vanderwinden ◽  
Christophe Erneux
Keyword(s):  
Cell Lines ◽  
Cancer Cell ◽  
Mitotic Spindle ◽  
Focal Adhesions ◽  
Cancer Cell Lines

scholarly journals A Novel Integrin-Linked Kinase–Binding Protein, Affixin, Is Involved in the Early Stage of Cell–Substrate Interaction

2001 ◽  
Vol 153 (6) ◽  
pp. 1251-1264 ◽  
Author(s):  
Satoshi Yamaji ◽  
Atsushi Suzuki ◽  
Yuki Sugiyama ◽  
Yu-ichi Koide ◽  
Michihiko Yoshida ◽  
...  
Keyword(s):  
Early Stage ◽  
Binding Protein ◽  
Focal Adhesions ◽  
Leading Edge ◽  
Cell Spreading ◽  
Substrate Interaction ◽  
Substrate Adhesion ◽  
Cell Substrate ◽  
Integrin Linked Kinase

Focal adhesions (FAs) are essential structures for cell adhesion, migration, and morphogenesis. Integrin-linked kinase (ILK), which is capable of interacting with the cytoplasmic domain of β1 integrin, seems to be a key component of FAs, but its exact role in cell–substrate interaction remains to be clarified. Here, we identified a novel ILK-binding protein, affixin, that consists of two tandem calponin homology domains. In CHOcells, affixin and ILK colocalize at FAs and at the tip of the leading edge, whereas in skeletal muscle cells they colocalize at the sarcolemma where cells attach to the basal lamina, showing a striped pattern corresponding to cytoplasmic Z-band striation. When CHO cells are replated on fibronectin, affixin and ILK but not FA kinase and vinculin concentrate at the cell surface in blebs during the early stages of cell spreading, which will grow into membrane ruffles on lamellipodia. Overexpression of the COOH-terminal region of affixin, which is phosphorylated by ILK in vitro, blocks cell spreading at the initial stage, presumably by interfering with the formation of FAs and stress fibers. The coexpression of ILK enhances this effect. These results provide evidence suggesting that affixin is involved in integrin–ILK signaling required for the establishment of cell–substrate adhesion.

scholarly journals A Novel Role for Integrin-linked Kinase in Epithelial Sheet Morphogenesis

2005 ◽  
Vol 16 (9) ◽  
pp. 4084-4095 ◽  
Author(s):  
Alisa Vespa ◽  
Sudhir J.A. D'Souza ◽  
Lina Dagnino
Keyword(s):  
Cell Membrane ◽  
Adherens Junction ◽  
Focal Adhesions ◽  
Cell Junctions ◽  
Keratinocyte Differentiation ◽  
Epidermal Keratinocytes ◽  
Cell Periphery ◽  
Integrin Linked Kinase ◽  
E Cadherin ◽  
Cell Cell

Integrin-linked kinase (ILK) is a multidomain protein involved in cell motility and cell-extracellular matrix interactions. ILK is found in integrin-containing focal adhesions in undifferentiated primary epidermal keratinocytes. Induction of keratinocyte differentiation by treatment with Ca2+ triggers formation of cell–cell junctions, loss of focal adhesions, and ILK distribution to cell borders. We now show that Ca2+ treatment of keratinocytes induces rapid (≤1 h) translocation to the cell membrane of the adherens junction (AJ) proteins E-cadherin and β-catenin. This is followed by slower (>6 h) localization of tight junction (TJ) proteins. The kinetics of ILK movement toward the cell periphery mimics that of AJ components, suggesting that ILK plays a role in the early formation of cell–cell contacts. Whereas the N terminus in ILK mediates localization to cell borders, expression of an ILK deletion mutant incapable of localizing to the cell membrane (ILK 191-452) interferes with translocation of E-cadherin/β-catenin to cell borders, precluding Ca2+-induced AJ formation. Cells expressing ILK 191-452 also fail to form TJ and sealed cell–cell borders and do not form epithelial sheets. Thus, we have uncovered a novel role for ILK in epithelial cell–cell adhesion, independent of its well-established role in integrin-mediated adhesion and migration.

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