Research Topics
Genomes and Genes
| Joseph SchlessingerSummaryAffiliation: Yale University Country: USA Publications
Research Grants
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Detail Information
Publications
On the nature of low- and high-affinity EGF receptors on living cellsFerruh Ozcan
Department of Pharmacology, Yale University School of Medicine, 333 Cedar Street, New Haven, CT 06520, USA
Proc Natl Acad Sci U S A 103:5735-40. 2006....
A solid base for assaying protein kinase activityJoseph Schlessinger
Department of Pharmacology, Yale University School of Medicine, New Haven, CT 06520, USA
Nat Biotechnol 20:232-3. 2002- SH2 and PTB domains in tyrosine kinase signalingJoseph Schlessinger
Department of Pharmacology, Yale University School of Medicine, New Haven, CT 06520, USA
Sci STKE 2003:RE12. 2003.... - Signal transduction. Autoinhibition controlJoseph Schlessinger
Department of Pharmacology, Yale University School of Medicine, New Haven, CT 06520, USA
Science 300:750-2. 2003 - Common and distinct elements in cellular signaling via EGF and FGF receptorsJoseph Schlessinger
Department of Pharmacology, Yale University School of Medicine, New Haven, CT 06520, USA
Science 306:1506-7. 2004..The differential circuitry of the intracellular networks that are activated by EGFR and FGFR may affect signal specificity and physiological responses... - Ligand-induced, receptor-mediated dimerization and activation of EGF receptorJoseph Schlessinger
Department of Pharmacology, Yale University School of Medicine, New Haven, CT 06520, USA
Cell 110:669-72. 2002..Receptor dimerization is mediated by receptor-receptor interactions in which a loop protruding from neighboring receptors mediates receptor dimerization and activation... - Nuclear signaling by receptor tyrosine kinases: the first robin of springJoseph Schlessinger
Department of Pharmacology, Yale University School of Medicine, New Haven, CT 06520, USA
Cell 127:45-8. 2006..The fragment forms a complex with the adaptor TAB2 and the corepressor N-CoR and transits to the nucleus, where it represses transcription of genes that promote the formation of astrocytes... - The docking protein FRS2alpha controls a MAP kinase-mediated negative feedback mechanism for signaling by FGF receptorsIrit Lax
Department of Pharmacology, Yale University School of Medicine, New Haven, CT 06520, USA
Mol Cell 10:709-19. 2002..These experiments reveal a novel MAPK-mediated, negative feedback mechanism for control of signaling pathways that are dependent on FRS2 and a mechanism for heterologous control of signaling via FGF receptors... - Suppression of EGFR endocytosis by dynamin depletion reveals that EGFR signaling occurs primarily at the plasma membraneLeiliane P Sousa
Departments of Pharmacology, Yale University School of Medicine, New Haven, CT 06520, USA
Proc Natl Acad Sci U S A 109:4419-24. 2012.... - Structural basis for reduced FGFR2 activity in LADD syndrome: Implications for FGFR autoinhibition and activationErin D Lew
Department of Pharmacology, Yale University School of Medicine, 333 Cedar Street, New Haven, CT 06510, USA
Proc Natl Acad Sci U S A 104:19802-7. 2007.... 
The docking protein Gab1 is the primary mediator of EGF-stimulated activation of the PI-3K/Akt cell survival pathwayDawn R Mattoon
Department of Pharmacology, Yale University School of Medicine, PO Box 208066, New Haven, CT 06520 8066, USA
BMC Biol 2:24. 2004..As the autophosphorylation sites on EGF-receptor (EGFR) do not include canonical PI-3 kinase binding sites, it is thought that EGF stimulation of PI-3 kinase and its downstream effector Akt is mediated by an indirect mechanism...- The docking protein Gab1 is an essential component of an indirect mechanism for fibroblast growth factor stimulation of the phosphatidylinositol 3-kinase/Akt antiapoptotic pathwayBetty Lamothe
Department of Pharmacology, Yale University School of Medicine, 333 Cedar St, SHM B 295, New Haven, CT 06520, USA
Mol Cell Biol 24:5657-66. 2004.... - Asymmetric receptor contact is required for tyrosine autophosphorylation of fibroblast growth factor receptor in living cellsJae Hyun Bae
Department of Pharmacology, Yale University School of Medicine, 333 Cedar Street, New Haven, CT 06520, USA
Proc Natl Acad Sci U S A 107:2866-71. 2010..The experiments presented in this report provide the molecular basis underlying the control of transphosphorylation of FGF receptors and other receptor tyrosine kinases... - A structure-based model for ligand binding and dimerization of EGF receptorsPeter Klein
Department of Pharmacology, Yale University School of Medicine, 333 Cedar Street, New Haven, CT 06520, USA
Proc Natl Acad Sci U S A 101:929-34. 2004..However, these extended receptors do not correspond directly with the "high-affinity" EGF-binding sites seen in EGF-binding studies on intact cells... - The precise sequence of FGF receptor autophosphorylation is kinetically driven and is disrupted by oncogenic mutationsErin D Lew
Department of Pharmacology, Yale University School of Medicine, 333 Cedar Street, New Haven, CT 06520, USA
Sci Signal 2:ra6. 2009..We propose that disrupted stepwise activation of tyrosine autophosphorylation caused by oncogenic and other activating FGFR mutations may lead to aberrant activation of and assembly of signaling molecules by the activated receptor... - Direct contacts between extracellular membrane-proximal domains are required for VEGF receptor activation and cell signalingYan Yang
Department of Pharmacology, Yale University School of Medicine, 333 Cedar Street, New Haven, CT 06520, USA
Proc Natl Acad Sci U S A 107:1906-11. 2010..It also reveals a conserved mechanism for RTK activation and a novel target for pharmacological intervention of pathologically activated RTKs... - Structural basis for activation of the receptor tyrosine kinase KIT by stem cell factorSatoru Yuzawa
Department of Pharmacology, Yale University School of Medicine, 333 Cedar Street, New Haven, CT 06520, USA
Cell 130:323-34. 2007.... - Contacts between membrane proximal regions of the PDGF receptor ectodomain are required for receptor activation but not for receptor dimerizationYan Yang
Department of Pharmacology, Yale University School of Medicine, 333 Cedar Street, New Haven, CT 06520, USA
Proc Natl Acad Sci U S A 105:7681-6. 2008..Moreover, PDGFRbeta dimerization is necessary but not sufficient for tyrosine kinase activation... 
The selectivity of receptor tyrosine kinase signaling is controlled by a secondary SH2 domain binding siteJae Hyun Bae
Department of Pharmacology, Yale University School of Medicine, 333 Cedar Street, New Haven, CT 06520, USA
Cell 138:514-24. 2009..These experiments reveal a mechanism for how SH2 domain selectivity is regulated in vivo to mediate a specific cellular process...- Asymmetric tyrosine kinase arrangements in activation or autophosphorylation of receptor tyrosine kinasesJae Hyun Bae
Department of Pharmacology, Yale University School of Medicine, 333 Cedar St, New Haven, CT 06520 8066, USA
Mol Cells 29:443-8. 2010..These studies demonstrate that asymmetric dimer formation is as a common phenomenon critical for activation and autophosphorylation of RTKs... - Activation of the nonreceptor protein tyrosine kinase Ack by multiple extracellular stimuliMaria L Galisteo
Department of Pharmacology, Yale University School of Medicine, New Haven, CT 06520, USA
Proc Natl Acad Sci U S A 103:9796-801. 2006..These experiments suggest a functional role for Ack as an early transducer of multiple extracellular stimuli... - Constitutive activated Cdc42-associated kinase (Ack) phosphorylation at arrested endocytic clathrin-coated pits of cells that lack dynaminHongying Shen
Department of Cell Biology, Howard Hughes Medical Institute, Program in Cellular Neuroscience, Neurodegeneration and Repair, and Kavli Institute for Neuroscience, Yale University School of Medicine, New Haven, CT 06510, USA
Mol Biol Cell 22:493-502. 2011..These findings reveal a link between progression of clathrin-coated pits to endocytic vesicles and an activation-deactivation cycle of Ack... - [Structural biology of receptor tyrosine kinase kit]Satornu Yuzawa
Yale University School of Medicine, 333 Cedar Street, New Haven, CT 06520, USA
Seikagaku 80:94-104. 2008 - Crystal structures of free and ligand-bound focal adhesion targeting domain of Pyk2James Lulo
Department of Pharmacology, Yale University School of Medicine, New Haven, CT 06520, USA
Biochem Biophys Res Commun 383:347-52. 2009.... - Discovery of novel fibroblast growth factor receptor 1 kinase inhibitors by structure-based virtual screeningKrishna P Ravindranathan
Department of Chemistry, Yale University, New Haven, Connecticut 06520, USA
J Med Chem 53:1662-72. 2010..The study also illustrates complexities associated with the choice of protein structures for docking, possible use of multiple kinase structures to seek selectivity, and hit identification... - The tethered configuration of the EGF receptor extracellular domain exerts only a limited control of receptor functionDawn Mattoon
Department of Pharmacology, Yale University School of Medicine, 333 Cedar Street, New Haven, CT 06520, USA
Proc Natl Acad Sci U S A 101:923-8. 2004..Furthermore, the autoinhibition conferred by the tethered configuration of the extracellular ligand-binding domain provides only a limited control of EGFR function... - All signaling is local?Joseph Schlessinger
Department of Pharmacology, Yale University School of Medicine, New Haven, CT 06510, USA
Mol Cell 10:218-9. 2002..Recent studies have visualized the spatio-temporal pattern of EGF signaling, indicating that receptor density is an important factor in the mechanism of lateral propagation of local EGF signaling... - FRS2 family docking proteins with overlapping roles in activation of MAP kinase have distinct spatial-temporal patterns of expression of their transcriptsNoriko Gotoh
Department of Pharmacology, Yale University School of Medicine, Sterling Hall of Medicine, 333 Cedar Street, B 204, New Haven, CT 06520, USA
FEBS Lett 564:14-8. 2004..We propose that the FRS2 family proteins have distinct roles in vivo through activation of common signaling proteins including MAP kinase... - Lacrimo-auriculo-dento-digital syndrome is caused by reduced activity of the fibroblast growth factor 10 (FGF10)-FGF receptor 2 signaling pathwayImad Shams
Department of Pharmacology, Yale University School of Medicine, New Haven, CT 06520, USA
Mol Cell Biol 27:6903-12. 2007.... - Autophosphorylation of FGFR1 kinase is mediated by a sequential and precisely ordered reactionCristina M Furdui
Department of Pharmacology, Yale University School of Medicine, New Haven, Connecticut 06520, USA
Mol Cell 21:711-7. 2006.... - Type II p21-activated kinases (PAKs) are regulated by an autoinhibitory pseudosubstrateByung Hak Ha
Department of Pharmacology, Yale University School of Medicine, New Haven, CT 06520, USA
Proc Natl Acad Sci U S A 109:16107-12. 2012..Finally, we find Src SH3, but not β-PIX SH3, can activate PAK4. We provide a unique understanding for type II PAK regulation... - FRS2 alpha attenuates FGF receptor signaling by Grb2-mediated recruitment of the ubiquitin ligase CblAndy Wong
Department of Pharmacology, Sterling Hall of Medicine, Yale University School of Medicine, 333 Cedar Street, New Haven, CT 06520, USA
Proc Natl Acad Sci U S A 99:6684-9. 2002..However, the partial inhibition of FGF receptor down-regulation in FRS2 alpha-/- cells indicates that the attenuation of signaling by FGF receptor is regulated by redundant or multiple mechanisms... - FGFR3-targeted mAb therapy for bladder cancer and multiple myelomaYaron Hadari
Kolltan Pharmaceuticals Inc, New Haven, Connecticut, USA
J Clin Invest 119:1077-9. 2009..These results suggest that clinical development of anti-FGFR3 mAbs should be considered for targeted therapy of cancer and other diseases... - A critical role for the protein tyrosine phosphatase receptor type Z in functional recovery from demyelinating lesionsSheila Harroch
Department of Pharmacology, Yale University School of Medicine, New Haven, Connecticut 06520, USA
Nat Genet 32:411-4. 2002..These results support a role for Ptprz in oligodendrocyte survival and in recovery from demyelinating disease... - Defective microtubule-dependent podosome organization in osteoclasts leads to increased bone density in Pyk2(-/-) miceHava Gil-Henn
Department of Pharmacology, Yale University School of Medicine, New Haven, CT 06511, USA
J Cell Biol 178:1053-64. 2007..These experiments underscore an important role of Pyk2 in microtubule-dependent podosome organization, bone resorption, and other osteoclast functions... - Epidermal growth factor receptor dimerization and activation require ligand-induced conformational changes in the dimer interfaceJessica P Dawson
Department of Biochemistry and Biophysics, University of Pennsylvania School of Medicine, Philadelphia, 19104 6059, USA
Mol Cell Biol 25:7734-42. 2005..Our data also suggest that similar conformational changes may determine the specificity of ErbB receptor homo- versus heterodimerization... - A putative molecular-activation switch in the transmembrane domain of erbB2Sarel J Fleishman
Department of Biochemistry, The George S Wise Faculty of Life Sciences, Tel Aviv University, Ramat Aviv 69987, Israel Middle East
Proc Natl Acad Sci U S A 99:15937-40. 2002.... - Receptor protein tyrosine phosphatase gamma is a marker for pyramidal cells and sensory neurons in the nervous system and is not necessary for normal developmentSmaragda Lamprianou
Institut Pasteur, Department of Neuroscience, 25 rue du Dr Roux, 75724 Paris, France
Mol Cell Biol 26:5106-19. 2006..An initial behavioral analysis showed minor changes in the RPTPgamma-null mice... - Insights into the molecular basis for fibroblast growth factor receptor autoinhibition and ligand-binding promiscuityShaun K Olsen
Departments of Pharmacology and Microbiology, New York University School of Medicine, New York, NY 10016, USA
Proc Natl Acad Sci U S A 101:935-40. 2004..Importantly, comparison of the three FGF1-FGFR structures shows that the flexibility of the betaC'-betaE loop is a major determinant of ligand-binding specificity and promiscuity... - Trans-activation of EphA4 and FGF receptors mediated by direct interactions between their cytoplasmic domainsHideyuki Yokote
Department of Molecular Cell Biology, Institute of Advanced Medicine, Wakayama Medical University, 811 1 Kimiidera, Wakayama 641 8509, Japan
Proc Natl Acad Sci U S A 102:18866-71. 2005.... - A family of phosphodiesterase inhibitors discovered by cocrystallography and scaffold-based drug designGraeme L Card
Plexxikon Inc, 91 Bolivar Dr, Berkeley, California 94710, USA
Nat Biotechnol 23:201-7. 2005.... - Structural basis for the activity of drugs that inhibit phosphodiesterasesGraeme L Card
Plexxikon, Inc, 91 Bolivar Drive, Berkeley, CA 94710, USA
Structure 12:2233-47. 2004..These structural insights will enable the design of isoform-selective inhibitors with improved binding affinity and should facilitate the discovery of more potent and selective PDE inhibitors for the treatment of a variety of diseases... - A glutamine switch mechanism for nucleotide selectivity by phosphodiesterasesKam Y J Zhang
Plexxikon Inc, 91 Bolivar Drive, Berkeley, CA 94710, USA
Mol Cell 15:279-86. 2004..The structural understanding of nucleotide binding enables the design of new PDE inhibitors that may treat diseases in which cyclic nucleotides play a critical role... - Discovery of a selective inhibitor of oncogenic B-Raf kinase with potent antimelanoma activityJames Tsai
Plexxikon, Inc, 91 Bolivar Drive, Berkeley, CA 94710, USA
Proc Natl Acad Sci U S A 105:3041-6. 2008.... - Mutations in different components of FGF signaling in LADD syndromeEdyta Rohmann
Center for Molecular Medicine Cologne, University of Cologne, 50931 Cologne, Germany
Nat Genet 38:414-7. 2006..These findings increase the spectrum of anomalies associated with abnormal FGF signaling... - 'Tuning' of type I interferon-induced Jak-STAT1 signaling by calcium-dependent kinases in macrophagesLu Wang
Arthritis and Tissue Degeneration Program, Hospital for Special Surgery, New York, New York 10021, USA
Nat Immunol 9:186-93. 2008..Our results associate Pyk2 and Jak kinases with the linkage of signals emanating from cytokine and heterologous ITAM-dependent receptors... - The biochemical response of the heart to hypertension and exerciseTetsuro Wakatsuki
Department of Biochemistry and Molecular Biophysics, Washington University School of Medicine, Washington University Medical Center, Campus Box 8231, 660 South Euclid Avenue, St Louis, MI 63110 1093, USA
Trends Biochem Sci 29:609-17. 2004..Despite this progress, the mechanisms that activate fibroblasts to cause fibrosis and those that differentiate between exercise and hypertension to produce physiological and pathological responses, respectively, remain to be established...
Research Grants
- FGF RECEPTOR SIGNALING IN BONE DEVELOPMENTJoseph Schlessinger; Fiscal Year: 2009....
- Docking protein FRS2 in FGF signalingJoseph Schlessinger; Fiscal Year: 2007..abstract_text> ..
- FGF RECEPTOR SIGNALING IN BONE DEVELOPMENTJoseph Schlessinger; Fiscal Year: 2007....