C. elegans PAT-4/ILK Functions as an Adaptor Protein within Integrin Adhesion Complexes

Mackinnon, Alexander C.; Qadota, Hiroshi; Norman, Kenneth R.; Moerman, Donald G.; Williams, Bruce A.

doi:10.1016/s0960-9822(02)00810-2

Cited by 285 publications

(321 citation statements)

References 44 publications

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“…MIG-2 is a widely expressed and evolutionarily conserved FA protein (17)(18)(19)(20)(21). The experiments presented in this study have demonstrated a specific interaction between MIG-2 and the ␤1 and ␤3 integrin cytoplasmic domains.…”

Section: Discussionmentioning

confidence: 54%

“…MIG-2 (mitogen-inducible gene-2, also known as kindlin-2) is a widely expressed and evolutionarily conserved cytoplasmic protein (17)(18)(19)(20)(21). Genetic studies have shown that Caenorhabditis elegans UNC-112, a homolog of MIG-2, is required for attachment of body-wall muscle cells to the hypodermis (17,19).…”

mentioning

confidence: 99%

“…Genetic studies have shown that Caenorhabditis elegans UNC-112, a homolog of MIG-2, is required for attachment of body-wall muscle cells to the hypodermis (17,19). Loss of UNC-112 in C. elegans results in an embryonic lethal Pat (paralyzed, arrested elongation at two-fold) phenotype resembling that of ␣ or ␤ integrin loss (17,19). In mammalian organisms, MIG-2 has been detected in many cell types, including fibroblasts, muscle cells, endothelial cells, and epithelial cells (20,22).…”

mentioning

confidence: 99%

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The MIG-2/Integrin Interaction Strengthens Cell-Matrix Adhesion and Modulates Cell Motility

Shi

Qing

et al. 2007

Journal of Biological Chemistry

162

176

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Integrin-mediated cell-matrix adhesion plays an important role in control of cell behavior. We report here that MIG-2, a widely expressed focal adhesion protein, interacts with ␤1 and ␤3 integrin cytoplasmic domains. Integrin binding is mediated by a single site within the MIG-2 FERM domain. Functionally, the MIG-2/integrin interaction recruits MIG-2 to focal adhesions. Furthermore, using ␣IIb␤3 integrin-expressing Chinese hamster ovary cells, a well described model system for integrin activation, we show that MIG-2 promotes integrin activation and enhances cell-extracellular matrix adhesion. Although MIG-2 is expressed in many cell types, it is deficient in certain colon cancer cells. Expression of MIG-2, but not of an integrin binding-defective MIG-2 mutant, in MIG-2-null colon cancer cells strengthened cell-matrix adhesion, promoted focal adhesion formation, and reduced cell motility. These results suggest that the MIG-2/integrin interaction is an important element in the cellular control of integrin-mediated cell-matrix adhesion and that loss of this interaction likely contributes to high motility of colon cancer cells.Cell-extracellular matrix (ECM) 3 adhesion is a fundamental process that is mediated by transmembrane receptors such as integrins (1-6). The interactions of integrins with ECM ligands can be controlled by integrin activation via "inside-out" signaling. Talin, a FERM (Band 4.1 (four point one)/ezrin/radixin/ moesin) domain-containing focal adhesion (FA) protein, can play a key role in this process (for recent reviews, see Refs. 7-10). Binding of the talin FERM domain to the ␤ integrin cytoplasmic domains results in separation of the ␣ and ␤ integrin cytoplasmic tails and consequently in an increase in integrin extracellular ligand-binding affinity (i.e. integrin activation) (11-13). Integrin extracellular ligand-binding affinity plays an important role in control of initial cell-ECM adhesion. Additionally, integrin-mediated cell-ECM adhesion can be enhanced through interactions with cytoskeletal proteins, a process that has been termed cytoskeletal strengthening (14 -16). The physical basis underlying the cytoskeletal strengthening of cell-ECM adhesion has been well described (16). However, the molecular interactions that mediate this process remain to be defined.MIG-2 (mitogen-inducible gene-2, also known as kindlin-2) is a widely expressed and evolutionarily conserved cytoplasmic protein (17-21). Genetic studies have shown that Caenorhabditis elegans UNC-112, a homolog of MIG-2, is required for attachment of body-wall muscle cells to the hypodermis (17,19). Loss of UNC-112 in C. elegans results in an embryonic lethal Pat (paralyzed, arrested elongation at two-fold) phenotype resembling that of ␣ or ␤ integrin loss (17, 19). In mammalian organisms, MIG-2 has been detected in many cell types, including fibroblasts, muscle cells, endothelial cells, and epithelial cells (20,22). In these cells, it concentrates at FAs. MIG-2 interacts with migfilin (20), a filamin-and VASP (vasodilatorstimulated p...

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Section: Discussionmentioning

confidence: 54%

mentioning

confidence: 99%

mentioning

confidence: 99%

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The MIG-2/Integrin Interaction Strengthens Cell-Matrix Adhesion and Modulates Cell Motility

Shi

Qing

et al. 2007

Journal of Biological Chemistry

162

176

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“…Both of these proteins have emerged as evolutionarily conserved mediators of integrin-actin linkages in muscle tissue. Together with the LIM-only adaptor protein PINCH and possibly Nck2, ILK and actopaxin are required for normal muscle development and integrinactin attachment in organisms as diverse as flies and worms (147,164,327). Although a role for paxillin in mammalian muscle cytoarchitecture is clear, the contribution played by this protein in lower organisms remains to be determined.…”

Section: Integrin-actin Linkages and Muscle Contractionmentioning

confidence: 99%

Paxillin: Adapting to Change

Brown¹,

Turner²

2004

Physiological Reviews

550

728

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Molecular scaffold or adaptor proteins facilitate precise spatiotemporal regulation and integration of multiple signaling pathways to effect the optimal cellular response to changes in the immediate environment. Paxillin is a multidomain adaptor that recruits both structural and signaling molecules to focal adhesions, sites of integrin engagement with the extracellular matrix, where it performs a critical role in transducing adhesion and growth factor signals to elicit changes in cell migration and gene expression.

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“…20 Interestingly, UNC-112 also interacts with the homolog of integrin-linked kinase or ILK. 21 In view of the similarity between this protein and MIG2, we have named this protein MIG2B. MIG2B was 52% identical and 76% homologous to MIG2 at the protein level.…”

Section: Identification and Characterization Of Mig2bmentioning

confidence: 99%

Proteomic analysis of the cell-surface membrane in chronic lymphocytic leukemia: identification of two novel proteins, BCNP1 and MIG2B

et al. 2003

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B-cell-specific plasma-membrane proteins are potential targets for either small molecule or antibody-based therapies. We have sought to annotate proteins expressed at the cell surface membrane in patients with chronic lymphocytic leukemia (CLL) using plasma-membrane-based proteomic analysis to identify previously uncharacterized and potentially B-cell-specific proteins. Proteins from plasma-membrane fractions were separated on one-dimensional gels and trypsinized fractions subjected to high-throughput MALDI-TOF mass spectrometry. Using this method, many known B-cell surface antigens were detected, but also known proteins not previously described in this disease or in this cellular compartment, including cell surface receptors, membrane-associated enzymes and secreted proteins, and completely unknown proteins. To validate the method, we show that BLK, a B-cell-specific kinase, is located in the CLL-plasma-membrane fraction. We also describe two novel proteins (MIG2B and B-cell novel protein #1, BCNP1), which are expressed preferentially in B cells. MIG2B is in a highly conserved and defined gene family containing two plasma-membrane-binding ezrin/radixin/moesin domains and a pleckstrin homology domain; the Caenorhabditis elegans homolog (UNC-112) is a membrane-associated protein that colocalizes with integrin at cell-matrix adhesion complexes. BCNP1 is a completely unknown protein with three predicted transmembrane domains, with three alternatively spliced final exons. Proteomic analysis may thus define new potential therapeutic targets.

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C. elegans PAT-4/ILK Functions as an Adaptor Protein within Integrin Adhesion Complexes

Abstract: Our data strengthens the emerging view that ILK functions primarily as an adaptor protein within integrin adhesion complexes and identifies UNC-112 as a new ILK binding partner.

Cited by 285 publications

References 44 publications

The MIG-2/Integrin Interaction Strengthens Cell-Matrix Adhesion and Modulates Cell Motility

The MIG-2/Integrin Interaction Strengthens Cell-Matrix Adhesion and Modulates Cell Motility

Paxillin: Adapting to Change

Proteomic analysis of the cell-surface membrane in chronic lymphocytic leukemia: identification of two novel proteins, BCNP1 and MIG2B

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