Other search tools

About this data

The publication data currently available has been vetted by Vanderbilt faculty, staff, administrators and trainees. The data itself is retrieved directly from NCBI's PubMed and is automatically updated on a weekly basis to ensure accuracy and completeness.

If you have any questions or comments, please contact us.

Results: 31 to 40 of 41

Publication Record

Connections

Integrin-dependent PLC-gamma1 phosphorylation mediates fibronectin-dependent adhesion.
Tvorogov D, Wang XJ, Zent R, Carpenter G
(2005) J Cell Sci 118: 601-10
MeSH Terms: Animals, Cell Adhesion, Cell Line, Cell Movement, Fibroblasts, Fibronectins, Focal Adhesion Kinase 1, Focal Adhesion Protein-Tyrosine Kinases, Integrin beta1, Integrins, Mice, Mice, Knockout, Phospholipase C gamma, Phosphorylation, Protein Binding, Protein-Tyrosine Kinases, Type C Phospholipases, Tyrosine, src-Family Kinases
Show Abstract · Added December 10, 2013
Although integrin engagement initiates signaling events such as focal-adhesion kinase (FAK) and Src kinase activation, the role of phosphoinositide turnover in cell adhesion is less clear. To assess PLC-gamma1 function in this process, Plcg1(-/-) fibroblasts (Null) were compared with the same fibroblasts in which PLC-gamma1 was re-expressed (Null+). Following plating on fibronectin, Null cells displayed a significantly impaired rate of adhesion compared with Null+ cells. This defect was detected at low concentrations of fibronectin; at high fibronectin concentrations, the Null and Null+ cells displayed equivalent adhesion characteristics. The differences were not due to PLC-gamma1-dependent changes in integrin subunit expression, nor was integrin receptor clustering impaired with the absence of PLC-gamma1. Experiments with site-specific antibodies and PLC-gamma1 mutants showed that fibronectin selectively increased phosphorylation of Tyr783 and that mutagenesis of this residue, but not Tyr771 or Tyr1253, abrogated fibronectin-dependent adhesion. The SH2 domains of PLC-gamma1 were also required for maximal adhesion on fibronectin. Adhesion to fibronectin induced PLC-gamma1 tyrosine phosphorylation that was inhibited by a Src-kinase inhibitor, but not an epidermal-growth-factor-receptor kinase inhibitor. Moreover, in cells null for Src family members, but not in cells null for FAK family members, integrin-dependent PLC-gamma1 tyrosine phosphorylation was greatly reduced. Finally, the data demonstrated that PLC-gamma1 co-immunoprecipitated with Src following fibronectin-induced integrin activation, and this association did not depend on FAK expression.
1 Communities
1 Members
0 Resources
19 MeSH Terms
CD98hc (SLC3A2) interaction with beta 1 integrins is required for transformation.
Henderson NC, Collis EA, Mackinnon AC, Simpson KJ, Haslett C, Zent R, Ginsberg M, Sethi T
(2004) J Biol Chem 279: 54731-41
MeSH Terms: Animals, Antigens, CD, Antigens, Differentiation, T-Lymphocyte, CHO Cells, Cell Division, Cell Membrane, Cell Transformation, Neoplastic, Cricetinae, Drug Interactions, Fluorescent Antibody Technique, Fusion Regulatory Protein 1, Heavy Chain, Gene Expression, Humans, Integrin beta1, Lectins, C-Type, Microscopy, Confocal, Peptide Fragments, Phosphatidylinositol 3-Kinases, Recombinant Fusion Proteins, Signal Transduction, Structure-Activity Relationship, Transfection
Show Abstract · Added December 10, 2013
CD98hc (SLC3A2) constitutively and specifically associates with beta(1) integrins and is highly expressed on the surface of human tumor cells irrespective of the tissue of origin. We have found here that expression of CD98hc promotes both anchorage- and serum-independent growth. This oncogenic activity is dependent on beta(1) integrin-mediated phosphoinositol 3-hydroxykinase stimulation and the level of surface expression of CD98hc. Using chimeras of CD98hc and the type II membrane protein CD69, we show that the transmembrane domain of CD98hc is necessary and sufficient for integrin association in cells. Furthermore, CD98hc/beta(1) integrin association is required for focal adhesion kinase-dependent phosphoinositol 3-hydroxykinase activation and cellular transformation. Amino acids 82-87 in the putative cytoplasmic/transmembrane region appear to be critical for the oncogenic potential of CD98hc and provide a novel mechanism for tumor promotion by integrins. These results explain how high expression of CD98hc in human cancers contributes to transformation; furthermore, the transmembrane association of CD98hc and beta(1) integrins may provide a new target for cancer therapy.
1 Communities
1 Members
0 Resources
22 MeSH Terms
Overexpression of HER2 (erbB2) in human breast epithelial cells unmasks transforming growth factor beta-induced cell motility.
Ueda Y, Wang S, Dumont N, Yi JY, Koh Y, Arteaga CL
(2004) J Biol Chem 279: 24505-13
MeSH Terms: Actins, Activin Receptors, Type I, Adenoviridae, Antibodies, Monoclonal, Antibodies, Monoclonal, Humanized, Blotting, Northern, Breast Neoplasms, Bromodeoxyuridine, Butadienes, Cell Cycle, Cell Division, Cell Line, Cell Line, Tumor, Cell Movement, Chromones, DNA, Complementary, Disease Progression, Enzyme Inhibitors, Epithelial Cells, Gene Expression Regulation, Genes, Reporter, Green Fluorescent Proteins, Humans, Imidazoles, Immunoblotting, Integrin beta1, Ligands, Luminescent Proteins, Microscopy, Fluorescence, Models, Genetic, Morpholines, Nitriles, Phosphatidylinositol 3-Kinases, Precipitin Tests, Protein-Serine-Threonine Kinases, Pseudopodia, Pyridines, Receptor, ErbB-2, Receptor, Transforming Growth Factor-beta Type I, Receptors, Transforming Growth Factor beta, Retroviridae, Signal Transduction, Transcription, Genetic, Transforming Growth Factor beta, Trastuzumab, Wound Healing, rac1 GTP-Binding Protein
Show Abstract · Added March 5, 2014
We have examined overexpression of the human epidermal growth factor receptor 2 (HER2) to determine if it modifies the anti-proliferative effect of transforming growth factor (TGF)-beta against MCF-10A human mammary epithelial cells. Exogenous TGF-beta inhibited cell proliferation and induced Smad-dependent transcriptional reporter activity in both MCF-10A/HER2 and MCF-10A/vector control cells. Ligand-induced reporter activity was 7-fold higher in HER2-overexpressing cells. In wound closure and transwell assays, TGF-beta induced motility of HER2-transduced, but not control cells. The HER2-blocking antibody trastuzumab (Herceptin) prevented TGF-beta-induced cell motility. Expression of a constitutively active TGF-beta type I receptor (ALK5(T204D)) induced motility of MCF-10A/HER2 but not MCF-10A/vector cells. TGF-beta-induced motility was blocked by coincubation with either the phosphatidylinositol 3-kinase inhibitor LY294002, the mitogen-activated protein kinase (MAPK) inhibitor U0126, the p38 MAPK inhibitor SB202190, and an integrin beta(1) blocking antibody. Rac1 activity was higher in HER2-overexpressing cells, where both Rac1 and Pak1 proteins were constitutively associated with HER2. Both exogenous TGF-beta and transduction with constitutively active ALK5 enhanced this association. TGF-beta induced actin stress fibers as well as lamellipodia within the leading edge of wounds. Herceptin blocked basal and TGF-beta-stimulated Rac1 activity but did not repress TGF-beta-stimulated transcriptional reporter activity. These data suggest that 1) overexpression of HER2 in nontumorigenic mammary epithelial is permissive for the ability of TGF-beta to induce cell motility and Rac1 activity, and 2) HER2 and TGF-beta signaling cooperate in the induction of cellular events associated with tumor progression.
0 Communities
1 Members
0 Resources
47 MeSH Terms
Tumor cell alpha3beta1 integrin and vascular laminin-5 mediate pulmonary arrest and metastasis.
Wang H, Fu W, Im JH, Zhou Z, Santoro SA, Iyer V, DiPersio CM, Yu QC, Quaranta V, Al-Mehdi A, Muschel RJ
(2004) J Cell Biol 164: 935-41
MeSH Terms: Animals, Antibodies, Basement Membrane, Blood Vessels, Cell Adhesion, Cell Adhesion Molecules, Cell Line, Tumor, Humans, Integrin alpha3, Integrin beta1, Ligands, Lung, Mice, Neoplasm Invasiveness, Neoplasm Metastasis, Neoplasms, Rats
Show Abstract · Added February 18, 2013
Arrest of circulating tumor cells in distant organs is required for hematogenous metastasis, but the tumor cell surface molecules responsible have not been identified. Here, we show that the tumor cell alpha3beta1 integrin makes an important contribution to arrest in the lung and to early colony formation. These analyses indicated that pulmonary arrest does not occur merely due to size restriction, and raised the question of how the tumor cell alpha3beta1 integrin contacts its best-defined ligand, laminin (LN)-5, a basement membrane (BM) component. Further analyses revealed that LN-5 is available to the tumor cell in preexisting patches of exposed BM in the pulmonary vasculature. The early arrest of tumor cells in the pulmonary vasculature through interaction of alpha3beta1 integrin with LN-5 in exposed BM provides both a molecular and a structural basis for cell arrest during pulmonary metastasis.
2 Communities
2 Members
0 Resources
17 MeSH Terms
Identification and isolation of candidate human colonic clonogenic cells based on cell surface integrin expression.
Fujimoto K, Beauchamp RD, Whitehead RH
(2002) Gastroenterology 123: 1941-8
MeSH Terms: Cell Adhesion, Cell Separation, Clone Cells, Colon, Extracellular Matrix Proteins, Flow Cytometry, Fluorescent Antibody Technique, Humans, Integrin beta1, Integrins, Membrane Proteins, Microvilli, Protein Isoforms, Stem Cells, Tissue Distribution
Show Abstract · Added June 14, 2013
BACKGROUND & AIMS - The surface epithelium of the colon is being replaced constantly with cells derived from the stem cells of the crypt. Although the location of the stem cells is known, there are no markers for these cells. This study tested the hypothesis that colonic stem cells might be isolated and cultured on the basis of specific integrin expression patterns in normal human colonic epithelium.
METHODS - Integrin expression in normal human colonic mucosa was determined by using indirect immunofluorescence. Crypt cells were then isolated as single cells from normal colon tissues and the expression pattern of integrins was analyzed by flow cytometry. Based on the specific expression of integrin beta1 in colonic crypts, the cells were sorted by using a flow cytometer, and colony assays in soft agar were performed to evaluate the clonogenicity of the sorted cells.
RESULTS - By immunofluorescence, the cells located in the lower one third of crypts expressed higher levels of beta1-integrin than the cells in the remainder of the crypt. When isolated crypt cells were stained with the beta1-integrin antibody and examined in a flow cytometer, there were 2 peaks of fluorescence. Sorting of crypt cells based on staining with anti-beta1 integrin antibody produced a cell population with a significantly enhanced ability to form colonies.
CONCLUSIONS - beta1-integrin is a candidate surface marker for the proliferative zone of the human colonic crypt. Our in vitro culture system for the clonal growth of a single colonic crypt cell suspension could facilitate the identification of other candidate stem cell markers.
1 Communities
1 Members
0 Resources
15 MeSH Terms
Integrin beta 1 signaling is necessary for transforming growth factor-beta activation of p38MAPK and epithelial plasticity.
Bhowmick NA, Zent R, Ghiassi M, McDonnell M, Moses HL
(2001) J Biol Chem 276: 46707-13
MeSH Terms: Cell Adhesion, Cell Differentiation, Cytoplasm, DNA, Complementary, Dose-Response Relationship, Drug, Ecdysterone, Enzyme Activation, Epithelial Cells, Extracellular Matrix, Genes, Dominant, Immunoblotting, Integrin beta1, Ligands, Mesoderm, Microscopy, Fluorescence, Mitogen-Activated Protein Kinases, Phenotype, Phosphorylation, Precipitin Tests, Protein Binding, Protein-Serine-Threonine Kinases, Receptor, Transforming Growth Factor-beta Type II, Receptors, Transforming Growth Factor beta, Signal Transduction, Spectrometry, Fluorescence, Time Factors, Transcriptional Activation, Transforming Growth Factor beta, p38 Mitogen-Activated Protein Kinases
Show Abstract · Added February 17, 2014
Transforming growth factor-beta (TGF-beta) can induce epithelial to mesenchymal transdifferentiation (EMT) in mammary epithelial cells. TGF-beta-mediated EMT involves the stimulation of a number of signaling pathways by the sequential binding of the type II and type I serine/threonine kinase receptors, respectively. Integrins comprise a family of heterodimeric extracellular matrix receptors that mediate cell adhesion and intracellular signaling, hence making them crucial for EMT progression. In light of substantial evidence indicating TGF-beta regulation of various beta(1) integrins and their extracellular matrix ligands, we examined the cross-talk between the TGF-beta and integrin signal transduction pathways. Using an inducible system for the expression of a cytoplasmically truncated dominant negative TGF-beta type II receptor, we blocked TGF-beta-mediated growth inhibition, transcriptional activation, and EMT progression. Dominant negative TGF-beta type II receptor expression inhibited TGF-beta signaling to the SMAD and AKT pathways, but did not block TGF-beta-mediated p38MAPK activation. Interestingly, blocking integrin beta(1) function inhibited TGF-beta-mediated p38MAPK activation and EMT progression. Limiting p38MAPK activity through the expression of a dominant negative-p38MAPK also blocked TGF-beta-mediated EMT. In summary, TGF-beta-mediated p38MAPK activation is dependent on functional integrin beta(1), and p38MAPK activity is required but is not sufficient to induce EMT.
1 Communities
2 Members
0 Resources
29 MeSH Terms
New functions for non-collagenous domains of human collagen type IV. Novel integrin ligands inhibiting angiogenesis and tumor growth in vivo.
Petitclerc E, Boutaud A, Prestayko A, Xu J, Sado Y, Ninomiya Y, Sarras MP, Hudson BG, Brooks PC
(2000) J Biol Chem 275: 8051-61
MeSH Terms: Amino Acid Sequence, Angiogenesis Inhibitors, Animals, Antigens, CD, Basement Membrane, Carcinoma, Cell Adhesion, Chick Embryo, Collagen, Endothelium, Vascular, Extraembryonic Membranes, Humans, Integrin alphaV, Integrin beta1, Integrins, Ligands, Melanoma, Models, Molecular, Molecular Sequence Data, Neovascularization, Pathologic, Peptide Fragments, Protein Structure, Tertiary, Urinary Bladder Neoplasms
Show Abstract · Added December 10, 2013
Collagen type IV is a major component of the basal lamina of blood vessels. Six genetically distinct collagen type IV chains have been identified and are distributed in a tissue-specific manner. Here we define a novel function for soluble non-collagenous (NC1) domains of the alpha2(IV), alpha3(IV), and alpha6(IV) chains of human collagen type IV in the regulation of angiogenesis and tumor growth. These NC1 domains were shown to regulate endothelial cell adhesion and migration by distinct alpha(v) and beta(1) integrin-dependent mechanisms. Systemic administration of recombinant alpha2(IV), alpha3(IV), and alpha6(IV) NC1 domains potently inhibit angiogenesis and tumor growth, whereas alpha1(IV), alpha4(IV), and alpha5(IV) showed little if any effect. These findings suggest that specific NC1 domains of collagen type IV may represent an important new class of angiogenesis inhibitors.
1 Communities
1 Members
0 Resources
23 MeSH Terms
Determinants of ligand binding specificity of the alpha(1)beta(1) and alpha(2)beta(1) integrins.
Dickeson SK, Mathis NL, Rahman M, Bergelson JM, Santoro SA
(1999) J Biol Chem 274: 32182-91
MeSH Terms: Amino Acid Sequence, Binding Sites, Cloning, Molecular, Collagen, Enzyme-Linked Immunosorbent Assay, Escherichia coli, Humans, Integrin alpha1beta1, Integrin beta1, Integrins, Ligands, Models, Molecular, Molecular Sequence Data, Protein Conformation, Receptors, Collagen, Structure-Activity Relationship
Show Abstract · Added March 5, 2014
The alpha(1)beta(1) and alpha(2)beta(1) integrins are cell surface collagen receptors. Cells expressing the alpha(1)beta(1) integrin preferentially adhere to collagen IV, whereas cells expressing the alpha(2)beta(1) integrin preferentially adhere to collagen I. Recombinant alpha(1) and alpha(2) integrin I domains exhibit the same collagen type preferences as the intact integrins. In addition, the alpha(2) integrin I domain binds echovirus 1; the alpha(1) I domain does not. To identify the structural components of the I domains responsible for the varying ligand specificities, we have engineered several alpha(1)/alpha(2) integrin I domain chimeras and evaluated their virus and collagen binding activities. Initially, large secondary structural components of the alpha(2) I domain were replaced with corresponding regions of the alpha(1) I domain. Following analysis in echovirus 1 and collagen binding assays, chimeras with successively smaller regions of alpha(1) I were constructed and analyzed. The chimeras were analyzed by ELISA with several different alpha(2) integrin monoclonal antibodies to assess their proper folding. Three different regions of the alpha(1) I domain, when present in the alpha(2) I domain, conferred enhanced collagen IV binding activity upon the alpha(2) I domain. These include the alpha3 and alpha5 helices and a portion of the alpha6 helix. Echovirus 1 binding was lost in a chimera containing the alphaC-alpha6 loop; higher resolution mapping identified Asn(289) as playing a critical role in echovirus 1 binding. Asn(289) had not been implicated in previous echovirus 1 binding studies. Taken together, these data reveal the existence of multiple determinants of ligand binding specificities within the alpha(1) and alpha(2) integrin I domains.
1 Communities
1 Members
0 Resources
16 MeSH Terms
The Talin head domain binds to integrin beta subunit cytoplasmic tails and regulates integrin activation.
Calderwood DA, Zent R, Grant R, Rees DJ, Hynes RO, Ginsberg MH
(1999) J Biol Chem 274: 28071-4
MeSH Terms: Amino Acid Sequence, Chromatography, Affinity, Cytoplasm, Humans, Integrin beta1, Molecular Sequence Data, Protein Binding, Protein Conformation, Recombinant Proteins, Talin
Show Abstract · Added December 10, 2013
The beta subunit cytoplasmic domains of integrin adhesion receptors are necessary for the connection of these receptors to the actin cytoskeleton. The cytoplasmic protein, talin, binds to beta integrin cytoplasmic tails and actin filaments, hence forming an integrin-cytoskeletal linkage. We used recombinant structural mimics of beta(1)A, beta(1)D and beta(3) integrin cytoplasmic tails to characterize integrin-binding sites within talin. Here we report that an integrin-binding site is localized within the N-terminal talin head domain. The binding of the talin head domain to integrin beta tails is specific in that it is abrogated by a single point mutation that disrupts integrin localization to talin-rich focal adhesions. Integrin-cytoskeletal interactions regulate integrin affinity for ligands (activation). Overexpression of a fragment of talin containing the head domain led to activation of integrin alpha(IIb)beta(3); activation was dependent on the presence of both the talin head domain and the integrin beta(3) cytoplasmic tail. The head domain of talin thus binds to integrins to form a link to the actin cytoskeleton and can thus regulate integrin function.
1 Communities
1 Members
0 Resources
10 MeSH Terms
Identification of a functionally important sequence in the cytoplasmic tail of integrin beta 3 by using cell-permeable peptide analogs.
Liu XY, Timmons S, Lin YZ, Hawiger J
(1996) Proc Natl Acad Sci U S A 93: 11819-24
MeSH Terms: Amino Acid Sequence, Antigens, CD, Biological Transport, Cell Adhesion, Cell Line, Endothelium, Vascular, Humans, Integrin beta1, Integrin beta3, Leukemia, Erythroblastic, Acute, Male, Molecular Sequence Data, Peptide Fragments, Peptides, Platelet Membrane Glycoproteins, Skin, Tumor Cells, Cultured
Show Abstract · Added December 10, 2013
Integrins are major two-way signaling receptors responsible for the attachment of cells to the extracellular matrix and for cell-cell interactions that underlie immune responses, tumor metastasis, and progression of atherosclerosis and thrombosis. We report the structure-function analysis of the cytoplasmic tail of integrin beta 3 (glycoprotein IIla) based on the cellular import of synthetic peptide analogs of this region. Among the four overlapping cell-permeable peptides, only the peptide carrying residues 747-762 of the carboxyl-terminal segment of integrin beta 3 inhibited adhesion of human erythroleukemia (HEL) cells and of human endothelial cells (ECV) 304 to immobilized fibrinogen mediated by integrin beta 3 heterodimers, alpha IIb beta 3, and alpha v beta 3, respectively. Inhibition of adhesion was integrin-specific because the cell-permeable beta 3 peptide (residues 747-762) did not inhibit adhesion of human fibroblasts mediated by integrin beta 1 heterodimers. Conversely, a cell-permeable peptide representing homologous portion of the integrin beta 1 cytoplasmic tail (residues 788-803) inhibited adhesion of human fibroblasts, whereas it was without effect on adhesion of HEL or ECV 304 cells. The cell-permeable integrin beta 3 peptide (residues 747-762) carrying a known loss-of-function mutation (Ser752Pro) responsible for the genetic disorder Glanzmann thrombasthenia Paris I did not inhibit cell adhesion of HEL or ECV 304 cells, whereas the beta 3 peptide carrying a Ser752Ala mutation was inhibitory. Although Ser752 is not essential, Tyr747 and Tyr759 form a functionally active tandem because conservative mutations Tyr747Phe or Tyr759Phe resulted in a nonfunctional cell permeable integrin beta 3 peptide. We propose that the carboxyl-terminal segment of the integrin beta 3 cytoplasmic tail spanning residues 747-762 constitutes a major intracellular cell adhesion regulatory domain (CARD) that modulates the interaction of integrin beta 3-expressing cells with immobilized fibrinogen. Import of cell-permeable peptides carrying this domain results in inhibition "from within" of the adhesive function of these integrins.
0 Communities
1 Members
0 Resources
17 MeSH Terms