Research Topics
Genomes and Genes | JOEL BENNETTSummaryAffiliation: University of Pennsylvania Country: USA Publications
Research Grants
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Publications
Agonist-activated alphavbeta3 on platelets and lymphocytes binds to the matrix protein osteopontinJ S Bennett
Hematology Oncology Division, Department of Medicine, The University of Pennsylvania School of Medicine, Philadelphia, Pennsylvania 19104, USA
J Biol Chem 272:8137-40. 1997..By inhibiting alphavbeta3 function, it may be possible to inhibit platelet-mediated vascular occlusion with a minimal effect on primary hemostasis...- The platelet cytoskeleton regulates the affinity of the integrin alpha(IIb)beta(3) for fibrinogenJ S Bennett
Department of Medicine, University of Pennsylvania, Philadelphia, Pennsylvania 19104, USA
J Biol Chem 274:25301-7. 1999..Increased actin filament turnover then relieves cytoskeletal constraints on alpha(IIb)beta(3), allowing it to assume the high affinity conformation required for soluble ligand binding... - Novel platelet inhibitorsJ S Bennett
Hematology Oncology Division, Department of Medicine, University of Pennsylvania School of Medicine, Philadelphia, Pennsylvania 19104, USA
Annu Rev Med 52:161-84. 2001..The efficacy of each type of alphaIIbbeta3 antagonist in the setting of acute coronary artery disease has been confirmed in multicenter clinical trials... - Effect of the Pl(A2) alloantigen on the function of beta(3)-integrins in plateletsJ S Bennett
Hematology Oncology Division, The Center for Experimental Therapeutics, and the General Clinical Research Center of the University of Pennsylvania School of Medicine, Philadelphia, Pennsylvania, USA
Blood 97:3093-9. 2001.... - Platelet-fibrinogen interactionsJ S Bennett
Hematology Oncology Division, Department of Medicine, University of Pennsylvania School of Medicine, Philadelphia, Pennsylvania, USA
Ann N Y Acad Sci 936:340-54. 2001..Nonetheless, there appears to be allosteric linkage between these sites, accounting for the ability of RGD-containing peptides to inhibit platelet aggregation and arterial thrombosis... 
The structure and function of platelet integrinsJ S Bennett
Hematology Oncology Division, Department of Medicine, University of Pennsylvania School of Medicine, Philadelphia, PA 19104, USA
J Thromb Haemost 7:200-5. 2009..This review focuses on the structure and function of the intensively studied beta3 integrins, in particular alphaIIbbeta3, but reference will be made to other integrins where relevant...
Structure and function of the platelet integrin alphaIIbbeta3Joel S Bennett
Hematology Oncology Division, Department of Medicine, University of Pennsylvania School of Medicine, Philadelphia, Pennsylvania 19104 6058, USA
J Clin Invest 115:3363-9. 2005..The biochemical, biophysical, and ultrastructural results that support this conclusion are discussed in this Review...- Activation of integrin alphaIIbbeta3 by modulation of transmembrane helix associationsRenhao Li
Department of Biochemistry and Biophysics, School of Medicine, University of Pennsylvania, Philadelphia, PA 19104, USA
Science 300:795-8. 2003..These results suggest that homomeric associations involving transmembrane domains provide a driving force for integrin activation. They also suggest a structural basis for the coincidence of integrin activation and clustering... - Activation of platelet alphaIIbbeta3 by an exogenous peptide corresponding to the transmembrane domain of alphaIIbHang Yin
Department of Biochemistry and Biophysics, School of Medicine, University of Pennsylvania, Philadelphia, Pennsylvania 19104, USA
J Biol Chem 281:36732-41. 2006..These observations demonstrate that transmembrane domain interactions regulate integrin function in situ and that it is possible to target intra-membranous protein-protein interactions in a way that can have functional consequences... - Computational design of peptides that target transmembrane helicesHang Yin
Department of Biochemistry and Biophysics, School of Medicine, University of Pennsylvania, Philadelphia, PA 19104, USA
Science 315:1817-22. 2007..These data show that sequence-specific recognition of helices in TM proteins can be achieved through optimization of the geometric complementarity of the target-host complex... - Interactions of ADP-stimulated human platelets with PEGylated polystyrene substrates prepared by surface amidationPen Cheng Wang
Hematology Oncology Division, Department of Medicine, School of Medicine, University of Pennsylvania, Philadelphia, PA 19104, USA
Colloids Surf B Biointerfaces 58:225-30. 2007..1 using H(2)N-PEG-NH(2)... - Dissociation of bimolecular αIIbβ3-fibrinogen complex under a constant tensile forceRustem I Litvinov
Department of Cell and Developmental Biology, University of Pennsylvania School of Medicine, Philadelphia, Pennsylvania, USA
Biophys J 100:165-73. 2011..Taken together, these data provide important quantitative and qualitative characteristics of αIIbβ3-fibrinogen binding and unbinding that underlie the dynamics of platelet adhesion and aggregation in blood flow... - Dimerization of the transmembrane domain of Integrin alphaIIb subunit in cell membranesRenhao Li
Department of Biochemistry and Biophysics and Hematology Oncology Division, University of Pennsylvania School of Medicine, Philadelphia, Pennsylvania 19104, USA
J Biol Chem 279:26666-73. 2004..Thus, although the alpha(IIb) TM helix makes use of the GXXXG framework, neighboring residues have evolved to engineer its dimerization interface, enabling it to subserve specific and specialized functions... - Quantitative analysis of platelet alpha v beta 3 binding to osteopontin using laser tweezersRustem I Litvinov
Department of Cell and Developmental Biology, University of Pennsylvania School of Medicine, Philadelphia, 19104 6058, USA
J Biol Chem 278:51285-90. 2003..Furthermore, they indicate that platelet adhesion to osteopontin-coated surfaces requires an agonist-induced exposure of alpha v beta 3-binding sites for this ligand... - Characterization of the monomeric form of the transmembrane and cytoplasmic domains of the integrin beta 3 subunit by NMR spectroscopyRenhao Li
Department of Biochemistry and Biophysics, Johnson Research Foundation, University of Pennsylvania School of Medicine, Philadelphia, PA 19104, USA
Biochemistry 41:15618-24. 2002..These structural features of the beta3 subunit should help to explain its interaction with numerous cytosolic interacting proteins and begin to illuminate the mechanism of integrin activation... - Activation of individual alphaIIbbeta3 integrin molecules by disruption of transmembrane domain interactions in the absence of clusteringRustem I Litvinov
Department of Cell and Developmental Biology, University of Pennsylvania School of Medicine, Philadelphia, Pennsylvania 19104, USA
Biochemistry 45:4957-64. 2006.... - Binding strength and activation state of single fibrinogen-integrin pairs on living cellsRustem I Litvinov
Department of Cell and Developmental Biology, University of Pennsylvania School of Medicine, Philadelphia, PA 19104-6058, USA
Proc Natl Acad Sci U S A 99:7426-31. 2002..This methodology can be applied to the study of other regulated cell membrane receptors using the ligand-receptor yield strength as a direct measure of receptor activation/inactivation state... - Multiple approaches converge on the structure of the integrin alphaIIb/beta3 transmembrane heterodimerDouglas G Metcalf
Department of Biochemistry and Biophysics, University of Pennsylvania, Philadelphia, PA 19104, USA
J Mol Biol 392:1087-101. 2009..These results demonstrate that multiple approaches converged on the same structure of the resting integrin's TM heterodimer, and this conformation likely reflects the integrin's native structure... - Arylamide derivatives as allosteric inhibitors of the integrin alpha2beta1/type I collagen interactionHang Yin
Department of Biochemistry and Biophysics, University of Pennsylvania School of Medicine, Philadelphia, 19104, USA
Bioorg Med Chem Lett 16:3380-2. 2006..Further we find that compound 4 recognizes a hydrophobic cleft on the side of the alpha(2) I-domain, suggesting an alternative targeting site for drug development... - Small molecule inhibitors of integrin alpha2beta1Sungwook Choi
Department of Biochemistry and Biophysics, University of Pennsylvania, Philadelphia, Pennsylvania 19104, USA
J Med Chem 50:5457-62. 2007.... - Consensus motif for integrin transmembrane helix associationBryan W Berger
Biochemistry and Biophysics, University of Pennsylvania School of Medicine, Philadelphia, PA 19104, USA
Proc Natl Acad Sci U S A 107:703-8. 2010..Thus, this highly conserved dissociable motif plays a vital and widespread role as an on-off switch that can integrate with other control elements during integrin activation... - Functional and structural correlations of individual alphaIIbbeta3 moleculesRustem I Litvinov
Department of Cell and Developmental Biology, University of Pennsylvania School of Medicine, 421 Curie Blvd, 1054 BRB II/III, Philadelphia, PA 19104-6058, USA
Blood 104:3979-85. 2004..Further, they are consistent with the presence of a linked equilibrium between single inactive and single active alphaIIbbeta3 molecules and active alphaIIbbeta3 clusters... - The design and evaluation of heparin-binding foldamersSungwook Choi
Department of Chemistry, University of Pennsylvania, Philadelphia, PA 19104-6323, USA
Angew Chem Int Ed Engl 44:6685-9. 2005 - Multi-step fibrinogen binding to the integrin (alpha)IIb(beta)3 detected using force spectroscopyRustem I Litvinov
Department of Cell and Developmental Biology, University of Pennsylvania School of Medicine, Philadelphia, PA 19104-6085, USA
Biophys J 89:2824-34. 2005..The aggregate of data provides evidence for complex multi-step binding/unbinding pathways of alphaIIbbeta3 and fibrinogen revealed at the single-molecule level... - Small-molecule inhibitors of integrin alpha2beta1 that prevent pathological thrombus formation via an allosteric mechanismMeredith W Miller
Department of Pharmacology, University of Pennsylvania, 1009 Stellar Chance Laboratories, 36th and Hamilton Walk, Philadelphia, PA 19104, USA
Proc Natl Acad Sci U S A 106:719-24. 2009..These results suggest that targeting integrin alpha(2)beta(1) could be a potentially safe, effective approach to long-term therapy for cardiovascular disease... - The relative role of PLCbeta and PI3Kgamma in platelet activationLurong Lian
Department of Medicine of University of Pennsylvania, 421 Curie Blvd, Biomedical Research Bldg II III, Rm 912, Philadelphia, PA 19104, USA
Blood 106:110-7. 2005..Nonetheless, the diminished ability of knock-out platelets to normally spread after adhesion and to form stable thrombi in vivo suggests that both PLCbeta2/beta3 and PI3Kgamma play vital roles in platelet cytoskeletal dynamics... - A key role for the integrin alpha2beta1 in experimental and developmental angiogenesisJames D San Antonio
Department of Pathology, Anatomy and Cell Biology, 1020 Locust Street, Thomas Jefferson University, Philadelphia, PA 19107, USA
Am J Pathol 175:1338-47. 2009..Collectively, our results provide strong biochemical and genetic evidence of a central role for alpha2beta1 integrin in experimental and developmental angiogenesis... - A push-pull mechanism for regulating integrin functionWei Li
Department of Medicine, Hematology-Oncology Division, School of Medicine, University of Pennsylvania, Philadelphia, PA 19104, USA
Proc Natl Acad Sci U S A 102:1424-9. 2005.... - Use of phage display to probe the evolution of binding specificity and affinity in integrinsRenhao Li
Department of Biochemistry and Biophysics, University of Pennsylvania School of Medicine, Philadelphia, PA 19104, USA
Protein Eng 16:65-72. 2003.... - Computationally designed peptide inhibitors of protein-protein interactions in membranesGregory A Caputo
Department of Chemistry and Biochemistry, University of Colorado, Boulder, Colorado 80309 0215, USA
Biochemistry 47:8600-6. 2008..These results demonstrate that CHAMP is a successful chemical biology approach that can provide specific tools for probing the transmembrane domains of proteins... - Vasoocclusion in sickle cell anemia: are platelets really involved?Joel S Bennett
Arterioscler Thromb Vasc Biol 26:1415-6. 2006 - Pro-thrombotic state induced by post-translational modification of fibrinogen by reactive nitrogen speciesCaryn Vadseth
Stokes Research Institute and Department of Biochemistry and Biophysics, Children's Hospital of Philadelphia, Philadelphia, PA 19104, USA
J Biol Chem 279:8820-6. 2004..The present results may account, in part, for the association between nitrative stress and risk for coronary artery disease...
Research Grants
- INTERACTION OF OSTEOPONTIN WITH ADHESION RECEPTORSJOEL BENNETT; Fiscal Year: 2002..Our results suggest that it may be possible to inhibit the formation of platelet thrombi in arteries involved by atherosclerosis by preventing the interaction of platelet alphavbeta3 with osteopontin. ..
- REGULATION OF PLATELET AND ENDOTHELIAL CELL FUNCTIONJOEL BENNETT; Fiscal Year: 2007..The five projects are supported by core facilities for the production of monoclonal antibodies and for the overall administration of the Program. ..