Talin: an emerging focal point of adhesion dynamics

Nayal, Anjana; Webb, Donna J.; Horwitz, Alan F.

doi:10.1016/j.ceb.2003.11.007

Cited by 152 publications

(116 citation statements)

References 53 publications

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“…Based on the known functions of the candidate genes, we can propose plausible roles in tumorigenesis, including deregulation of transduction of integrin signaling (TLN1) (Nayal et al, 2004), opposition to apoptosis (YAP1 and BIRC2), and adhesion and migration (TLN1, LAMA3, MMP7) (Lohi, 2001;Nayal et al, 2004). However, we were particularly interested in the observed amplification and overexpression of GLI2, JAG1, RBPSUH and FJX1, members of the hedgehog and notch pathways.…”

Section: Resultsmentioning

confidence: 99%

Rare amplicons implicate frequent deregulation of cell fate specification pathways in oral squamous cell carcinoma

et al. 2005

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Section: Resultsmentioning

confidence: 99%

Rare amplicons implicate frequent deregulation of cell fate specification pathways in oral squamous cell carcinoma

et al. 2005

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“…4 Thus, MIG-2 appears to interact with the membrane distal region rather than the membrane proximal region in the ␤3 integrin tail. It is widely accepted that interactions of talin-H with the membrane proximal region and consequently separation of the membrane proximal "clasp" are final intracellular steps in integrin activation (7)(8)(9)(11)(12)(13). On the other hand, the membrane distal region appears to regulate integrin activation indirectly (28,51).…”

Section: Discussionmentioning

confidence: 99%

“…The interaction of the talin FERM domain with the ␤ integrin tails has been extensively characterized (reviewed in Ref. [7][8][9][10]. Structurally, the talin-binding site encompasses both the membrane proximal and central regions of the ␤ integrin cytoplasmic tails (11,38,39) The first NPXY (Tyr 747 in the ␤3 integrin tail) site located in the central region of the ␤ integrin tails is crucial for the formation of the talin⅐␤ integrin complexes.…”

Section: Mig-2 Interacts With ␤1 and ␤3 Integrin Cytoplasmicmentioning

confidence: 99%

“…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][8][9][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.…”

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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“…This phosphorylation event is important for the efficient association of PIPKIg661 with talin and for localization to focal adhesions (Ling et al, 2003). Phosphatidyl inositol 4,5-bisphosphate (PIP 2 ), which is the product generated by phosphorylation of PIP by PIP kinases, regulates the interactions between a number of cytoskeletal proteins, including the association of talin with the cytoplasmic domains of the integrin b subunits and the binding of vinculin to talin (Nayal et al, 2004). Recruitment of PIPKIg661 to talin may promote local production of PIP 2 and consequently the assembly of protein complexes.…”

Section: Role Of Pipkic661mentioning

confidence: 99%

The interplay between Src and integrins in normal and tumor biology

2004

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Src family nonreceptor protein tyrosine kinases transduce signals that control normal cellular processes such as cell proliferation, adhesion and motility. Normally, cellular Src is held in an inactive state, but in several cancer types, abnormal events lead to elevated kinase activity of the protein and cause pleiotropic cellular responses inducing transformation and metastasis. A prerequisite of the ability of a cancer cell to undergo metastasis into distant tissues is to penetrate surrounding extracellular matrices. These processes are facilitated by the integrin family of cell adhesion molecules. As is the case with Src, altered integrin activity or substrate affinity can contribute to the neoplastic phenotype. Therefore, understanding the interplay between Src and integrin function has been of intense interest over the past few years. This review focuses on the role of Src and integrin signaling in normal cells and how this is deregulated in human cancer. We will identify the key players in the integrin-mediated signaling pathways involved in cell motility and apoptosis, such as FAK, paxillin and p130 CAS , and discuss how Src signaling affects the formation of focal adhesions and the extracellular matrix.

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Talin: an emerging focal point of adhesion dynamics

Cited by 152 publications

References 53 publications

Rare amplicons implicate frequent deregulation of cell fate specification pathways in oral squamous cell carcinoma

Rare amplicons implicate frequent deregulation of cell fate specification pathways in oral squamous cell carcinoma

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

The interplay between Src and integrins in normal and tumor biology

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