Research Topics
Genomes and Genes | S J ShattilSummaryAffiliation: The Scripps Research Institute Country: USA Publications
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Publications
Not just another pretty face: regulation of platelet function at the cytoplasmic face of integrin alpha IIb beta 3S J Shattil
Department of Vascular Biology, Scripps Research Institute, La Jolla, CA 92037, USA
Thromb Haemost 78:220-5. 1997....- Signaling through platelet integrin alpha IIb beta 3: inside-out, outside-in, and sidewaysS J Shattil
Department of Vascular Biology, Scripps Research Institute, La Jolla, CA 92037, USA
Thromb Haemost 82:318-25. 1999 - All in the family: primary megakaryocytes for studies of platelet alphaIIbbeta3 signalingS J Shattil
Department of Vascular Biology, Scripps Research Institute, La Jolla, CA 92037, USA
Thromb Haemost 86:259-65. 2001.... - Activation of Syk protein tyrosine kinase through interaction with integrin beta cytoplasmic domainsD G Woodside
Department of Vascular Biology, The Scripps Research Institute, La Jolla, CA 92037, USA
Curr Biol 11:1799-804. 2001..Thus, the direct binding of Syk kinase to the integrin beta3 cytoplasmic tail is a novel and functionally significant mechanism for the regulation of this important non-receptor tyrosine kinase... 
Regulation of the pp72syk protein tyrosine kinase by platelet integrin alpha IIb beta 3J Gao
Department of Vascular Biology, Scripps Research Institute, La Jolla, CA 92037, USA
EMBO J 16:6414-25. 1997..Furthermore, there are fundamental differences in the activation of Syk by alpha IIb beta 3 and immune response receptors, suggesting a unique role for integrins in Syk function...- Rac recruits high-affinity integrin alphavbeta3 to lamellipodia in endothelial cell migrationW B Kiosses
Department of Vascular Biology, 10550 North Torrey Pines Road, La Jolla, California 92037, USA
Nat Cell Biol 3:316-20. 2001..By using WOW-1, we have identified the selective recruitment of high-affinity integrins as a mechanism by which lamellipodia promote formation of new adhesions at the leading edge in cell migration... - A role for PKCtheta in outside-in alpha(IIb)beta3 signalingA Soriani
Division of Hematology Oncology, Department of Medicine, University of California San Diego, La Jolla, CA, USA
J Thromb Haemost 4:648-55. 2006..Thus, PKCtheta is a newly identified, essential member of a dynamic outside-in signaling complex that includes Btk and that couples alpha(IIb)beta3 to the actin cytoskeleton... - What is vinculin needed for in platelets?J V Mitsios
Department of Medicine, University of California, San Diego, La Jolla, CA 92093 0726, USA
J Thromb Haemost 8:2294-304. 2010..Conclusion: Despite promoting membrane cytoskeleton integrity when mechanical force is applied to α(IIb) β(3) , vinculin is not required for the traditional functions of α(IIb) β(3) or the platelet actin cytoskeleton... - Integrin activation controls metastasis in human breast cancerB Felding-Habermann
Department of Molecular and Experimental Medicine, The Scripps Research Institute, La Jolla, CA 92037, USA
Proc Natl Acad Sci U S A 98:1853-8. 2001..Consequently, alterations within tumors that lead to the aberrant control of integrin activation are expected to adversely affect the course of human breast cancer... 
The beta3 integrin cytoplasmic tail: protein scaffold and control freakS J Shattil
Division of Hematology Oncology, Department of Medicine, University of California San Diego, La Jolla, CA 92093 0726, USA
J Thromb Haemost 7:210-3. 2009..We speculate that this scaffold or its interacting proteins may serve as therapeutic targets for the development of future anti-thrombotic drugs...- Signaling networks linking integrins and rho family GTPasesM A Schwartz
Dept of Vascular Biology, The Scripps Research Institute, La Jolla, CA 92037, USA
Trends Biochem Sci 25:388-91. 2000..Recently, it has also become apparent that integrins regulate Rho GTPases and vice versa. Integrins and GTPases might therefore be organized into complex signaling cascades that regulate cell behavior... - Activation of integrins in endothelial cells by fluid shear stress mediates Rho-dependent cytoskeletal alignmentE Tzima
Department of Vascular Biology, The Scripps Research Institute, 10550 N.Torrey Pines Road, La Jolla, CA 92037, USA
EMBO J 20:4639-47. 2001..This transient inhibition is necessary for cytoskeletal alignment in the direction of flow. The results therefore define the role of integrins and Rho in a pathway leading to endothelial cell adaptation to flow... - Affinity modulation of platelet integrin alphaIIbbeta3 by beta3-endonexin, a selective binding partner of the beta3 integrin cytoplasmic tailH Kashiwagi
Department of Vascular Biology, The Scripps Research Institute, La Jolla, California 92037, USA
J Cell Biol 137:1433-43. 1997..By analogy, the adhesive function of platelets may be regulated by such protein-protein interactions at the level of the cytoplasmic tails of alphaIIbbeta3... - EGFR-dependent pancreatic carcinoma cell metastasis through Rap1 activationM Huang
Department of Pathology, Moores University of California San Diego Cancer Center, La Jolla, CA 92093 1503, USA
Oncogene 31:2783-93. 2012..These findings identify a molecular pathway that promotes the invasive/metastatic properties of human pancreatic carcinomas driven by EGFR... - Mechanisms and consequences of agonist-induced talin recruitment to platelet integrin alphaIIbbeta3Naohide Watanabe
Department of Medicine, University of California, San Diego, La Jolla, CA 92093, USA
J Cell Biol 181:1211-22. 2008..Thus, talin recruitment to alphaIIbbeta3 by RIAM mediates agonist-induced alphaIIbbeta3 activation, with implications for hemostasis and thrombosis... - PTP-1B is an essential positive regulator of platelet integrin signalingElena Garcia Arias-Salgado
Department of Medicine, University of California, San Diego, La Jolla, CA 92093, USA
J Cell Biol 170:837-45. 2005..Thus, PTP-1B is an essential positive regulator of the initiation of outside-in alphaIIbbeta3 signaling in platelets... - Caspase-12: a developmental link between G-protein-coupled receptors and integrin alphaIIbbeta3 activationSteven W Kerrigan
Department of Laboratory Medicine, University of California San Francisco, 513 Parnassus Ave, Rm S 577, San Francisco, CA 94143 0100, USA
Blood 104:1327-34. 2004.... - Signaling through GP Ib-IX-V activates alpha IIb beta 3 independently of other receptorsAna Kasirer-Friede
Department of Cell Biology, The Scripps Research Institute, 10550 N Torrey Pines Rd, La Jolla, CA 92037, USA
Blood 103:3403-11. 2004..These data establish that GP Ib-IX-V itself can signal to activate alpha IIb beta 3, through sequential actions of Src kinases, Ca(2+) oscillations, and PI 3-kinase/PKC... - Lateral clustering of platelet GP Ib-IX complexes leads to up-regulation of the adhesive function of integrin alpha IIbbeta 3Ana Kasirer-Friede
Departments of Cell Biology and Molecular and Experimental Medicine, The Scripps Research Institute, La Jolla, California 92037, USA
J Biol Chem 277:11949-56. 2002..By extrapolation, GP Ib-IX clustering in platelets may promote thrombus formation... - Relationships between Rap1b, affinity modulation of integrin alpha IIbbeta 3, and the actin cytoskeletonAlessandra Bertoni
Department of Cell Biology, The Scripps Research Institute, La Jolla, California 92037, USA
J Biol Chem 277:25715-21. 2002..These studies establish that Rap1b can augment agonist-induced ligand binding to alpha(IIb)beta(3) through effects on integrin affinity, possibly by modulating alpha(IIb)beta(3) interactions with the actin cytoskeleton... - Differential role of glycolipid-enriched membrane domains in glycoprotein VI- and integrin-mediated phospholipase Cgamma2 regulation in plateletsPeter Wonerow
Department of Pharmacology, University of Oxford, Mansfield Road, Oxford OX1 3QT, UK
Biochem J 364:755-65. 2002.... - Coordinate interactions of Csk, Src, and Syk kinases with [alpha]IIb[beta]3 initiate integrin signaling to the cytoskeletonAchim Obergfell
Division of Vascular Biology, Department of Cell Biology, The Scripps Research Institute, La Jolla, CA 92037, USA
J Cell Biol 157:265-75. 2002..These studies establish that platelet spreading on fibrinogen requires sequential activation of Src and Syk in proximity to alphaIIbbeta3, thus providing a paradigm for initiation of integrin signaling to the actin cytoskeleton... - Talin binding to integrin beta tails: a final common step in integrin activationSeiji Tadokoro
Department of Cell Biology, The Scripps Research Institute, The Burnham Institute, La Jolla, CA 92037, USA
Science 302:103-6. 2003..Thus, regulated binding of talin to integrin beta tails is a final common element of cellular signaling cascades that control integrin activation... - The antithrombotic potential of selective blockade of talin-dependent integrin alpha IIb beta 3 (platelet GPIIb-IIIa) activationBrian G Petrich
Department of Medicine, UCSD School of Medicine, La Jolla, California 92093 0726, USA
J Clin Invest 117:2250-9. 2007..Furthermore, they suggest that modulation of beta(3) integrin-talin interactions may provide an attractive target for antithrombotics and result in a reduced risk of pathological bleeding... - Platelet integrin adhesive functions and signalingNicolas Prevost
Division of Hematology Oncology, Department of Medicine, University of California, San Diego, La Jolla, California, USA
Methods Enzymol 426:103-15. 2007..The present chapter details the various protocols and reagents currently in use in our laboratory to study alphaIIbbeta3 adhesive responses and signaling in both human and murine cell models... - Roles of focal adhesion kinase (FAK) in megakaryopoiesis and platelet function: studies using a megakaryocyte lineage specific FAK knockoutIan S Hitchcock
Department of Medicine, University of California San Diego, La Jolla 92093, USA
Blood 111:596-604. 2008..These studies establish clear roles for FAK in megakaryocyte growth and platelet function, setting the stage for manipulation of this component of the Tpo signaling apparatus for therapeutic benefit... - Microfluidic devices for studies of shear-dependent platelet adhesionEdgar Gutierrez
Department of Physics, University of California San Diego, La Jolla, CA 92093, USA
Lab Chip 8:1486-95. 2008..Because of small sample volumes required, the devices could be employed in research with genetically-modified model organisms and for adhesion tests in clinical settings with blood from neonates... - The GPIIb/IIIa (integrin alphaIIbbeta3) odyssey: a technology-driven saga of a receptor with twists, turns, and even a bendBarry S Coller
Laboratory of Blood and Vascular Biology, The Rockefeller University, New York, NY, USA
Blood 112:3011-25. 2008.... - Differential requirement for LAT and SLP-76 in GPVI versus T cell receptor signalingBarbi A Judd
Program in Molecular Biology, University of Iowa, Iowa City, IA 52242, USA
J Exp Med 195:705-17. 2002.... - Platelet integrins and immunoreceptorsAna Kasirer-Friede
Department of Medicine, University of California, San Diego, La Jolla, CA 92093 0726, USA
Immunol Rev 218:247-64. 2007.... - The oligodendrocyte precursor mitogen PDGF stimulates proliferation by activation of alpha(v)beta3 integrinsWia Baron
Department of Medical Genetics, University of Cambridge, and Cambridge Centre for Brain Repair, ED Adrian Building, University Forvie Site, Cambridge CB2 2PY, UK
EMBO J 21:1957-66. 2002.... - Reconstructing and deconstructing agonist-induced activation of integrin alphaIIbbeta3Jaewon Han
Department of Medicine, University of California, San Diego, La Jolla, California 92093, USA
Curr Biol 16:1796-806. 2006.... - Src kinase activation by direct interaction with the integrin beta cytoplasmic domainElena G Arias-Salgado
Department of Cell Biology, The Scripps Research Institute, La Jolla, CA 92037, USA
Proc Natl Acad Sci U S A 100:13298-302. 2003..The data provide a paradigm for integrin regulation of Src and a molecular basis for the similar functional defects of osteoclasts or platelets from mice lacking beta3 integrins or c-Src... - Detection of integrin alpha IIbbeta 3 clustering in living cellsCharito Buensuceso
Departments of Cell Biology and Molecular and Experimental Medicine, The Scripps Research Institute, La Jolla, California 92037, USA
J Biol Chem 278:15217-24. 2003..These studies in living cells establish that alpha(IIb)beta(3) clustering is modulated by fibrinogen and actin dynamics. More broadly, they should facilitate investigations of the mechanisms and consequences of integrin clustering... - Megakaryocytes derived from embryonic stem cells implicate CalDAG-GEFI in integrin signalingKoji Eto
Departments of Cell Biology and Molecular and Experimental Medicine, The Scripps Research Institute, La Jolla, CA 92037, USA
Proc Natl Acad Sci U S A 99:12819-24. 2002..01). These results establish that ES cells are a ready source of mature megakaryocytes for integrin studies and other biological applications, and they implicate CalDAG-GEFI in inside-out signaling to alphaIIbbeta3... - Proximal, selective, and dynamic interactions between integrin alphaIIbbeta3 and protein tyrosine kinases in living cellsMaddalena de Virgilio
Department of Cell Biology, The Scripps Research Institute, 10550 North Torrey Pines Rd, VB-5, La Jolla, CA 92037, USA
J Cell Biol 165:305-11. 2004..Thus, alphaIIbbeta3 interacts proximally, if not directly, with tyrosine kinases in a coordinated, selective, and dynamic manner during sequential phases of alphaIIbbeta3 signaling to the actin cytoskeleton... - Integrins: dynamic scaffolds for adhesion and signaling in plateletsSanford J Shattil
Department of Cell Biology, The Scripps Research Institute, La Jolla, CA, USA
Blood 104:1606-15. 2004.... - Protein-protein interactions in platelet alphaIIbbeta3 signalingCharito S Buensuceso
Division of Hematology-Oncology, Department of Medicine, University of California San Diego, La Jolla, California 92093, USA
Semin Thromb Hemost 30:427-39. 2004..This review summarizes the known proteins that directly interact with alpha (IIb)bbeta (3) and provides an overview of their roles in integrin function... - Regulation of outside-in signaling in platelets by integrin-associated protein kinase C betaCharito S Buensuceso
Hematology-Oncology Division, Department of Medicine, University of California San Diego, La Jolla, California 92093, USA
J Biol Chem 280:644-53. 2005..Furthermore, the studies extend the concept of alpha(IIb)beta(3) as a scaffold for multiple protein kinases that regulate the platelet actin cytoskeleton... - Amino acid changes in Drosophila alphaPS2betaPS integrins that affect ligand affinityThomas A Bunch
Department of Molecular and Cellular Biology, Arizona Cancer Center, Tucson, Arizona 85724, USA
J Biol Chem 281:5050-7. 2006..These studies establish a means to evaluate mechanisms and consequences of integrin affinity modulation in a tractable model genetic system... - ADAP is required for normal alphaIIbbeta3 activation by VWF/GP Ib-IX-V and other agonistsAna Kasirer-Friede
Department of Medicine, University of California San Diego, La Jolla 92093 0726, USA
Blood 109:1018-25. 2007..These studies establish ADAP as a component of inside-out signaling pathways that couple GP Ib-IX-V and other platelet agonist receptors to alphaIIbbeta3 activation...