Michael J. Eck, MD, PhD

Michael J. Eck, MD, PhD

Researcher

Contact Information

Office Phone Number

(617) 632-5860

Fax

(617) 632-4393

Biography

Michael J. Eck, MD, PhD

Dr. Eck received his M.D. and Ph.D. from the University of Texas Southwestern Medical School in 1991. He trained as a postdoctoral fellow with Dr. Stephen Harrison at Children’s Hospital and Harvard Medical School before joining the DFCI in 1996. Dr. Eck is currently Professor of Biological Chemistry and Molecular Pharmacology at the Dana-Farber Cancer Institute and Harvard Medical School. His research focuses on the structure and regulation of tyrosine kinases in cancer and on structure-based approaches to discovery of novel inhibitors. The Eck lab also studies the structure of formin proteins and their role in assembling the actin cytoskeleton.

Researcher

Physician

Professor of Biological Chemistry and Molecular Pharmacology, Harvard Medical School

Recent Awards

  • Career Award in the Biomedical Sciences, Burroughs Wellcome Fund

    1997

  • Scholar Award, Leukemia and Lymphoma Society of America

    2002

  • World Class Scholar, Korean Ministry of Science and Technology, Korea University

    2009

  • AACR Team Science Award (DF/HCC Thoracic Oncology Research Team)

    2010

Research

    Structural Biology of Cell Signaling and Cancer

    We use biochemical and structural methods (primarily X-ray crystallography) to study the structure and regulation of tyrosine kinases that are important in cancer. We are especially interested in understanding how cancer-causing mutations lead to loss of normal kinase regulation, and in using structural approaches to develop new anticancer drugs. Active areas of investigation include: (1) the structure and regulation of Jak-family kinases and their interactions with cytokine receptors, (2) lung cancer-derived mutations in the epidermal growth factor receptor (EGFR), (3) the structural biology of focal adhesion kinase (FAK), and (4) formin proteins and their role in assembling the actin cytoskeleton.

    Jak family kinases are central mediators of cytokine signaling, and mutations and chromosomal translocations of Jaks lead to hematopoietic cancers.  In particular, the V617F mutation in Jak2 causes myeloproliferative neoplasms.  We have recently discovered how this mutation alters the conformation of a regulatory “pseudokinase” domain that is unique to Jak-family members, and we are working to understand how this signal is in turn transmitted to the kinase domain.  A long-term goal is to discover inhibitors that specifically inhibit this mutant, without interfering with the function of other Jaks in normal cells.  We are also working to understand how the erythropoietin receptor binds and regulates Jak2.

    Mutations in the EGFR tyrosine kinase are a common cause of non-small cell lung cancer. Our structural and biochemical studies have shown how several of these mutations activate the kinase and simultaneously alter its sensitivity to inhibitors such as the drug erlotinib.  We have extensively characterized the drug-resistant EGFR T790M mutant and with our collaborators at the Dana-Farber, we developed a novel inhibitor WZ4002 that is highly active against this mutant.

    Because FAK signaling is critical for cell migration, it is thought to play an important role in the invasiveness and metastasis of human tumors. We determined the structure of FAK, which shows how its catalytic activity is regulated by its N-terminal “FERM” region.  We are currently studying how this inhibitory interaction of the FERM domain is released to activate FAK.  Additionally, to facilitate development of drugs specifically targeting FAK, we have analyzed the structure of FAK in complex with a number of inhibitors.

    Finally, in addition to tyrosine kinases, the laboratory studies formins, a large family of proteins that direct the assembly of the actin cytoskeleton in response to activation by Rho family GTPases. We discovered the unique “tethered-dimer” architecture of the formin FH2 domain, which is especially adapted for its role in directly assembling linear actin filaments.  Additionally we are studying formin regulation and interactions with accessory proteins that allow formins to build distinct actin structures for particular cellular processes.

    Research Departments

    Publications

      • Publisher Correction: Cryo-EM structure of a RAS/RAF recruitment complex. Nat Commun. 2023 Sep 07; 14(1):5517. View in: Pubmed

      • Cryo-EM structure of a RAS/RAF recruitment complex. Nat Commun. 2023 07 29; 14(1):4580. View in: Pubmed

      • Oncogenic K-Ras suppresses global miRNA function. Mol Cell. 2023 07 20; 83(14):2509-2523.e13. View in: Pubmed

      • Structural elements that enable specificity for mutant EGFR kinase domains with next-generation small-molecule inhibitors. Methods Enzymol. 2023; 685:171-198. View in: Pubmed

      • Structure and RAF family kinase isoform selectivity of type II RAF inhibitors tovorafenib and naporafenib. J Biol Chem. 2023 05; 299(5):104634. View in: Pubmed

      • Macrocyclization of Quinazoline-Based EGFR Inhibitors Leads to Exclusive Mutant Selectivity for EGFR L858R and Del19. J Med Chem. 2022 12 08; 65(23):15679-15697. View in: Pubmed

      • Structural Basis for Inhibition of Mutant EGFR with Lazertinib (YH25448). ACS Med Chem Lett. 2022 Dec 08; 13(12):1856-1863. View in: Pubmed

      • PH domain-mediated autoinhibition and oncogenic activation of Akt. Elife. 2022 08 15; 11. View in: Pubmed

      • Structure of the MRAS-SHOC2-PP1C phosphatase complex. Nature. 2022 09; 609(7926):416-423. View in: Pubmed

      • Molecular basis for cooperative binding and synergy of ATP-site and allosteric EGFR inhibitors. Nat Commun. 2022 05 09; 13(1):2530. View in: Pubmed

      • A Novel HER2-Selective Kinase Inhibitor Is Effective in HER2 Mutant and Amplified Non-Small Cell Lung Cancer. Cancer Res. 2022 04 15; 82(8):1633-1645. View in: Pubmed

      • An allosteric inhibitor against the therapy-resistant mutant forms of EGFR in non-small cell lung cancer. Nat Cancer. 2022 04; 3(4):402-417. View in: Pubmed

      • Quinazolinones as allosteric fourth-generation EGFR inhibitors for the treatment of NSCLC. Bioorg Med Chem Lett. 2022 07 15; 68:128718. View in: Pubmed

      • Design of a "Two-in-One" Mutant-Selective Epidermal Growth Factor Receptor Inhibitor That Spans the Orthosteric and Allosteric Sites. J Med Chem. 2022 01 27; 65(2):1370-1383. View in: Pubmed

      • The structural basis of PTEN regulation by multi-site phosphorylation. Nat Struct Mol Biol. 2021 10; 28(10):858-868. View in: Pubmed

      • Allosteric MEK inhibitors act on BRAF/MEK complexes to block MEK activation. Proc Natl Acad Sci U S A. 2021 09 07; 118(36). View in: Pubmed

      • Comprehensive functional evaluation of variants of fibroblast growth factor receptor genes in cancer. NPJ Precis Oncol. 2021 Jul 16; 5(1):66. View in: Pubmed

      • A structural perspective on targeting the RTK/Ras/MAP kinase pathway in cancer. Protein Sci. 2021 08; 30(8):1535-1553. View in: Pubmed

      • The Eya1 Phosphatase Mediates Shh-Driven Symmetric Cell Division of Cerebellar Granule Cell Precursors. Dev Neurosci. 2020; 42(5-6):170-186. View in: Pubmed

      • Mutant-Selective Allosteric EGFR Degraders are Effective Against a Broad Range of Drug-Resistant Mutations. Angew Chem Int Ed Engl. 2020 08 17; 59(34):14481-14489. View in: Pubmed

      • The protein kinase Akt acts as a coat adaptor in endocytic recycling. Nat Cell Biol. 2020 08; 22(8):927-933. View in: Pubmed

      • Structural Basis for EGFR Mutant Inhibition by Trisubstituted Imidazole Inhibitors. J Med Chem. 2020 04 23; 63(8):4293-4305. View in: Pubmed

      • Discovery and Optimization of Dibenzodiazepinones as Allosteric Mutant-Selective EGFR Inhibitors. ACS Med Chem Lett. 2019 Nov 14; 10(11):1549-1553. View in: Pubmed

      • Architecture of autoinhibited and active BRAF-MEK1-14-3-3 complexes. Nature. 2019 11; 575(7783):545-550. View in: Pubmed

      • A driving test for oncogenic mutations. J Biol Chem. 2019 06 14; 294(24):9390-9391. View in: Pubmed

      • Single and Dual Targeting of Mutant EGFR with an Allosteric Inhibitor. Cancer Discov. 2019 07; 9(7):926-943. View in: Pubmed

      • Discovery and Structural Characterization of ATP-Site Ligands for the Wild-Type and V617F Mutant JAK2 Pseudokinase Domain. ACS Chem Biol. 2019 04 19; 14(4):587-593. View in: Pubmed

      • Discovery of a Highly Potent and Broadly Effective Epidermal Growth Factor Receptor and HER2 Exon 20 Insertion Mutant Inhibitor. Angew Chem Int Ed Engl. 2018 09 03; 57(36):11629-11633. View in: Pubmed

      • Micro-nano-bio acoustic system for the detection of foodborne pathogens in real samples. Biosens Bioelectron. 2018 Jul 15; 111:52-58. View in: Pubmed

      • Correction: MELK is an oncogenic kinase essential for mitotic progression in basal-like breast cancer cells. Elife. 2018 03 12; 7. View in: Pubmed

      • MELK is not necessary for the proliferation of basal-like breast cancer cells. Elife. 2017 09 19; 6. View in: Pubmed

      • Crystal Structure of Leiomodin 2 in Complex with Actin: A Structural and Functional Reexamination. Biophys J. 2017 Aug 22; 113(4):889-899. View in: Pubmed

      • CRKL Mediates p110ß-Dependent PI3K Signaling in PTEN-Deficient Cancer Cells. Cell Rep. 2017 07 18; 20(3):549-557. View in: Pubmed

      • Response Heterogeneity of EGFR and HER2 Exon 20 Insertions to Covalent EGFR and HER2 Inhibitors. Cancer Res. 2017 05 15; 77(10):2712-2721. View in: Pubmed

      • Domain-dependent effects of insulin and IGF-1 receptors on signalling and gene expression. Nat Commun. 2017 03 27; 8:14892. View in: Pubmed

      • Leveraging Gas-Phase Fragmentation Pathways for Improved Identification and Selective Detection of Targets Modified by Covalent Probes. Anal Chem. 2016 12 20; 88(24):12248-12254. View in: Pubmed

      • Mitotic MELK-eIF4B signaling controls protein synthesis and tumor cell survival. Proc Natl Acad Sci U S A. 2016 08 30; 113(35):9810-5. View in: Pubmed

      • Crystal Structure of the FERM-SH2 Module of Human Jak2. PLoS One. 2016; 11(5):e0156218. View in: Pubmed

      • Overcoming EGFR(T790M) and EGFR(C797S) resistance with mutant-selective allosteric inhibitors. Nature. 2016 06 02; 534(7605):129-32. View in: Pubmed

      • Data publication with the structural biology data grid supports live analysis. Nat Commun. 2016 Mar 07; 7:10882. View in: Pubmed

      • SPLINTS: small-molecule protein ligand interface stabilizers. Curr Opin Struct Biol. 2016 Apr; 37:115-22. View in: Pubmed

      • EGF-receptor specificity for phosphotyrosine-primed substrates provides signal integration with Src. Nat Struct Mol Biol. 2015 Dec; 22(12):983-90. View in: Pubmed

      • Development of Selective Covalent Janus Kinase 3 Inhibitors. J Med Chem. 2015 Aug 27; 58(16):6589-606. View in: Pubmed

      • Structure and mechanism of activity-based inhibition of the EGF receptor by Mig6. Nat Struct Mol Biol. 2015 Sep; 22(9):703-711. View in: Pubmed

      • Discovery of a BTK/MNK dual inhibitor for lymphoma and leukemia. Leukemia. 2016 Jan; 30(1):173-81. View in: Pubmed

      • Activity of the Type II JAK2 Inhibitor CHZ868 in B Cell Acute Lymphoblastic Leukemia. Cancer Cell. 2015 Jul 13; 28(1):29-41. View in: Pubmed

      • Structure of a Bud6/Actin Complex Reveals a Novel WH2-like Actin Monomer Recruitment Motif. Structure. 2015 Aug 04; 23(8):1492-1499. View in: Pubmed

      • EGFR Mutations and Resistance to Irreversible Pyrimidine-Based EGFR Inhibitors. Clin Cancer Res. 2015 Sep 01; 21(17):3913-23. View in: Pubmed

      • PARP1-driven poly-ADP-ribosylation regulates BRCA1 function in homologous recombination-mediated DNA repair. Cancer Discov. 2014 Dec; 4(12):1430-47. View in: Pubmed

      • Phosphatidylinositol 4,5-bisphosphate triggers activation of focal adhesion kinase by inducing clustering and conformational changes. Proc Natl Acad Sci U S A. 2014 Aug 05; 111(31):E3177-86. View in: Pubmed

      • Colon cancer-derived oncogenic EGFR G724S mutant identified by whole genome sequence analysis is dependent on asymmetric dimerization and sensitive to cetuximab. Mol Cancer. 2014 Jun 04; 13:141. View in: Pubmed

      • MELK is an oncogenic kinase essential for mitotic progression in basal-like breast cancer cells. Elife. 2014 May 20; 3:e01763. View in: Pubmed

      • JAK-cytokine receptor recognition, unboxed. Nat Struct Mol Biol. 2014 May; 21(5):431-3. View in: Pubmed

      • Inhibition of KRAS-driven tumorigenicity by interruption of an autocrine cytokine circuit. Cancer Discov. 2014 Apr; 4(4):452-65. View in: Pubmed

      • Structural, biochemical, and clinical characterization of epidermal growth factor receptor (EGFR) exon 20 insertion mutations in lung cancer. Sci Transl Med. 2013 Dec 18; 5(216):216ra177. View in: Pubmed

      • Cetuximab response of lung cancer-derived EGF receptor mutants is associated with asymmetric dimerization. Cancer Res. 2013 Nov 15; 73(22):6770-9. View in: Pubmed

      • Mechanism for activation of mutated epidermal growth factor receptors in lung cancer. Proc Natl Acad Sci U S A. 2013 Sep 17; 110(38):E3595-604. View in: Pubmed

      • Structure of a pseudokinase-domain switch that controls oncogenic activation of Jak kinases. Nat Struct Mol Biol. 2013 Oct; 20(10):1221-3. View in: Pubmed

      • Structure-guided inhibitor design expands the scope of analog-sensitive kinase technology. ACS Chem Biol. 2013 Sep 20; 8(9):1931-8. View in: Pubmed

      • Structure and ubiquitination-dependent activation of TANK-binding kinase 1. Cell Rep. 2013 Mar 28; 3(3):747-58. View in: Pubmed

      • Structure of the formin-interaction domain of the actin nucleation-promoting factor Bud6. Proc Natl Acad Sci U S A. 2012 Dec 11; 109(50):E3424-33. View in: Pubmed

      • Functional analysis of receptor tyrosine kinase mutations in lung cancer identifies oncogenic extracellular domain mutations of ERBB2. Proc Natl Acad Sci U S A. 2012 Sep 04; 109(36):14476-81. View in: Pubmed

      • Cyclic di-GMP sensing via the innate immune signaling protein STING. Mol Cell. 2012 Jun 29; 46(6):735-45. View in: Pubmed

      • EGFR in limbo. Cell. 2012 May 11; 149(4):735-7. View in: Pubmed

      • Functional characterization of an isoform-selective inhibitor of PI3K-p110ß as a potential anticancer agent. Cancer Discov. 2012 May; 2(5):425-33. View in: Pubmed

      • Genetic resistance to JAK2 enzymatic inhibitors is overcome by HSP90 inhibition. J Exp Med. 2012 Feb 13; 209(2):259-73. View in: Pubmed

      • EGFR exon 19 insertions: a new family of sensitizing EGFR mutations in lung adenocarcinoma. Clin Cancer Res. 2012 Mar 15; 18(6):1790-7. View in: Pubmed

      • Tyrosine phosphorylation of Rac1: a role in regulation of cell spreading. PLoS One. 2011; 6(12):e28587. View in: Pubmed

      • Structure and function of the interacting domains of Spire and Fmn-family formins. Proc Natl Acad Sci U S A. 2011 Jul 19; 108(29):11884-9. View in: Pubmed

      • Mutations in the DDR2 kinase gene identify a novel therapeutic target in squamous cell lung cancer. Cancer Discov. 2011 Jun; 1(1):78-89. View in: Pubmed

      • Crystal structure of a coiled-coil domain from human ROCK I. PLoS One. 2011 Mar 21; 6(3):e18080. View in: Pubmed

      • Binucleine 2, an isoform-specific inhibitor of Drosophila Aurora B kinase, provides insights into the mechanism of cytokinesis. ACS Chem Biol. 2010 Nov 19; 5(11):1015-20. View in: Pubmed

      • The FERM domain: organizing the structure and function of FAK. Nat Rev Mol Cell Biol. 2010 Nov; 11(11):802-14. View in: Pubmed

      • The neuroblastoma-associated F1174L ALK mutation causes resistance to an ALK kinase inhibitor in ALK-translocated cancers. Cancer Res. 2010 Dec 15; 70(24):10038-43. View in: Pubmed

      • Crystal structure of a complex between amino and carboxy terminal fragments of mDia1: insights into autoinhibition of diaphanous-related formins. PLoS One. 2010 Sep 30; 5(9). View in: Pubmed

      • Structural basis for the recognition of N-end rule substrates by the UBR box of ubiquitin ligases. Nat Struct Mol Biol. 2010 Oct; 17(10):1175-81. View in: Pubmed

      • Novel mutant-selective EGFR kinase inhibitors against EGFR T790M. Nature. 2009 Dec 24; 462(7276):1070-4. View in: Pubmed

      • Structural and mechanistic underpinnings of the differential drug sensitivity of EGFR mutations in non-small cell lung cancer. Biochim Biophys Acta. 2010 Mar; 1804(3):559-66. View in: Pubmed

      • [Palmar wrist arthroscopy for evaluation of concomitant carpal lesions in operative treatment of distal intraarticular radius fractures]. Handchir Mikrochir Plast Chir. 2009 Oct; 41(5):295-9. View in: Pubmed

      • The interplay of structural information and functional studies in kinase drug design: insights from BCR-Abl. Curr Opin Cell Biol. 2009 Apr; 21(2):288-95. View in: Pubmed

      • Crystal structures of the FAK kinase in complex with TAE226 and related bis-anilino pyrimidine inhibitors reveal a helical DFG conformation. PLoS One. 2008; 3(11):e3800. View in: Pubmed

      • The Skap-hom dimerization and PH domains comprise a 3'-phosphoinositide-gated molecular switch. Mol Cell. 2008 Nov 21; 32(4):564-75. View in: Pubmed

      • The T790M mutation in EGFR kinase causes drug resistance by increasing the affinity for ATP. Proc Natl Acad Sci U S A. 2008 Feb 12; 105(6):2070-5. View in: Pubmed

      • Spatial and temporal regulation of focal adhesion kinase activity in living cells. Mol Cell Biol. 2008 Jan; 28(1):201-14. View in: Pubmed

      • Bronchial and peripheral murine lung carcinomas induced by T790M-L858R mutant EGFR respond to HKI-272 and rapamycin combination therapy. Cancer Cell. 2007 Jul; 12(1):81-93. View in: Pubmed

      • Structural basis for the autoinhibition of focal adhesion kinase. Cell. 2007 Jun 15; 129(6):1177-87. View in: Pubmed

      • Structure of the FH2 domain of Daam1: implications for formin regulation of actin assembly. J Mol Biol. 2007 Jun 22; 369(5):1258-69. View in: Pubmed

      • Structure-guided development of affinity probes for tyrosine kinases using chemical genetics. Nat Chem Biol. 2007 Apr; 3(4):229-38. View in: Pubmed

      • Structures of lung cancer-derived EGFR mutants and inhibitor complexes: mechanism of activation and insights into differential inhibitor sensitivity. Cancer Cell. 2007 Mar; 11(3):217-27. View in: Pubmed

      • Mechanism and function of formins in the control of actin assembly. Annu Rev Biochem. 2007; 76:593-627. View in: Pubmed

      • Epidermal growth factor receptor variant III mutations in lung tumorigenesis and sensitivity to tyrosine kinase inhibitors. Proc Natl Acad Sci U S A. 2006 May 16; 103(20):7817-22. View in: Pubmed

      • Structure of the autoinhibitory switch in formin mDia1. Structure. 2006 Feb; 14(2):257-63. View in: Pubmed

      • Crystal structure of the FERM domain of focal adhesion kinase. J Biol Chem. 2006 Jan 06; 281(1):252-9. View in: Pubmed

      • Crystal structure of the Jak3 kinase domain in complex with a staurosporine analog. Blood. 2005 Aug 01; 106(3):996-1002. View in: Pubmed

      • Activating mutation in the tyrosine kinase JAK2 in polycythemia vera, essential thrombocythemia, and myeloid metaplasia with myelofibrosis. Cancer Cell. 2005 Apr; 7(4):387-97. View in: Pubmed

      • EGFR mutation and resistance of non-small-cell lung cancer to gefitinib. N Engl J Med. 2005 Feb 24; 352(8):786-92. View in: Pubmed

      • A case of metastasizing invasive hydatidiform mole. Is less--less good? Review of the literature with regard to adequate treatment. Eur J Gynaecol Oncol. 2005; 26(2):158-62. View in: Pubmed

      • Structure and regulation of Src family kinases. Oncogene. 2004 Oct 18; 23(48):7918-27. View in: Pubmed

      • Small molecule blockade of transcriptional coactivation of the hypoxia-inducible factor pathway. Cancer Cell. 2004 Jul; 6(1):33-43. View in: Pubmed

      • Identifying and characterizing a novel activating mutation of the FLT3 tyrosine kinase in AML. Blood. 2004 Sep 15; 104(6):1855-8. View in: Pubmed

      • FERM domain interaction promotes FAK signaling. Mol Cell Biol. 2004 Jun; 24(12):5353-68. View in: Pubmed

      • EGFR mutations in lung cancer: correlation with clinical response to gefitinib therapy. Science. 2004 Jun 04; 304(5676):1497-500. View in: Pubmed

      • SAP increases FynT kinase activity and is required for phosphorylation of SLAM and Ly9. Int Immunol. 2004 May; 16(5):727-36. View in: Pubmed

      • Crystal structures of a Formin Homology-2 domain reveal a tethered dimer architecture. Cell. 2004 Mar 05; 116(5):711-23. View in: Pubmed

      • A conserved mechanism for Bni1- and mDia1-induced actin assembly and dual regulation of Bni1 by Bud6 and profilin. Mol Biol Cell. 2004 Feb; 15(2):896-907. View in: Pubmed

      • Proteomics-based target identification: bengamides as a new class of methionine aminopeptidase inhibitors. J Biol Chem. 2003 Dec 26; 278(52):52964-71. View in: Pubmed

      • The SAP and SLAM families in immune responses and X-linked lymphoproliferative disease. Nat Rev Immunol. 2003 Oct; 3(10):813-21. View in: Pubmed

      • A zinc clasp structure tethers Lck to T cell coreceptors CD4 and CD8. Science. 2003 Sep 19; 301(5640):1725-8. View in: Pubmed

      • Structural basis of degradation signal recognition by SspB, a specificity-enhancing factor for the ClpXP proteolytic machine. Mol Cell. 2003 Jul; 12(1):75-86. View in: Pubmed

      • Structural basis for negative regulation of hypoxia-inducible factor-1alpha by CITED2. Nat Struct Biol. 2003 Jul; 10(7):504-12. View in: Pubmed

      • Assembling atomic resolution views of the immunological synapse. Curr Opin Immunol. 2003 Jun; 15(3):286-93. View in: Pubmed

      • Origins of peptide selectivity and phosphoinositide binding revealed by structures of disabled-1 PTB domain complexes. Structure. 2003 May; 11(5):569-79. View in: Pubmed

      • SAP couples Fyn to SLAM immune receptors. Nat Cell Biol. 2003 Feb; 5(2):155-60. View in: Pubmed

      • Homotetrameric structure of the SNAP-23 N-terminal coiled-coil domain. J Biol Chem. 2003 Apr 11; 278(15):13462-7. View in: Pubmed

      • Specificity in signaling by c-Yes. Front Biosci. 2003 Jan 01; 8:s185-205. View in: Pubmed

      • Structural basis for recruitment of CBP/p300 by hypoxia-inducible factor-1 alpha. Proc Natl Acad Sci U S A. 2002 Apr 16; 99(8):5367-72. View in: Pubmed

      • Mutant tyrosine kinases with unnatural nucleotide specificity retain the structure and phospho-acceptor specificity of the wild-type enzyme. Chem Biol. 2002 Jan; 9(1):25-33. View in: Pubmed

      • Structure of a human Tcf4-beta-catenin complex. Nat Struct Biol. 2001 Dec; 8(12):1053-7. View in: Pubmed

      • Structural basis for the interaction of the free SH2 domain EAT-2 with SLAM receptors in hematopoietic cells. EMBO J. 2001 Nov 01; 20(21):5840-52. View in: Pubmed

      • Mapping of epitopes in discoidin domain receptor 1 critical for collagen binding. J Biol Chem. 2001 Dec 07; 276(49):45952-8. View in: Pubmed

      • Characterization of SH2D1A missense mutations identified in X-linked lymphoproliferative disease patients. J Biol Chem. 2001 Sep 28; 276(39):36809-16. View in: Pubmed

      • Implications for familial hypercholesterolemia from the structure of the LDL receptor YWTD-EGF domain pair. Nat Struct Biol. 2001 Jun; 8(6):499-504. View in: Pubmed

      • Structure of the cooperative allosteric anthranilate synthase from Salmonella typhimurium. Nat Struct Biol. 2001 Mar; 8(3):243-7. View in: Pubmed

      • Structure of PAK1 in an autoinhibited conformation reveals a multistage activation switch. Cell. 2000 Aug 04; 102(3):387-97. View in: Pubmed

      • Structure of a WW domain containing fragment of dystrophin in complex with beta-dystroglycan. Nat Struct Biol. 2000 Aug; 7(8):634-8. View in: Pubmed

      • Adapting to multiple personalities: Cbl is also a RING finger ubiquitin ligase. Biochim Biophys Acta. 2000 Jul 31; 1471(1):M1-M12. View in: Pubmed

      • Crystal structures of the XLP protein SAP reveal a class of SH2 domains with extended, phosphotyrosine-independent sequence recognition. Mol Cell. 1999 Oct; 4(4):555-61. View in: Pubmed

      • The Cbl protooncoprotein: a negative regulator of immune receptor signal transduction. Immunol Today. 1999 Aug; 20(8):375-82. View in: Pubmed

      • Crystal structure of the pleckstrin homology-phosphotyrosine binding (PH-PTB) targeting region of insulin receptor substrate 1. Proc Natl Acad Sci U S A. 1999 Jul 20; 96(15):8378-83. View in: Pubmed

      • Crystal structures of c-Src reveal features of its autoinhibitory mechanism. Mol Cell. 1999 May; 3(5):629-38. View in: Pubmed

      • Structure of the amino-terminal domain of Cbl complexed to its binding site on ZAP-70 kinase. Nature. 1999 Mar 04; 398(6722):84-90. View in: Pubmed

      • Activation of the protein tyrosine phosphatase SHP2 via the interleukin-6 signal transducing receptor protein gp130 requires tyrosine kinase Jak1 and limits acute-phase protein expression. Biochem J. 1998 Nov 01; 335 ( Pt 3):557-65. View in: Pubmed

      • A Zn2+ ion links the cytoplasmic tail of CD4 and the N-terminal region of Lck. J Biol Chem. 1998 Jul 24; 273(30):18729-33. View in: Pubmed

      • Crystal structure of the tyrosine phosphatase SHP-2. Cell. 1998 Feb 20; 92(4):441-50. View in: Pubmed

      • Peptide and protein phosphorylation by protein tyrosine kinase Csk: insights into specificity and mechanism. Biochemistry. 1998 Jan 06; 37(1):165-72. View in: Pubmed

      • Impaired secretion of very low density lipoprotein-triglycerides by apolipoprotein E- deficient mouse hepatocytes. J Clin Invest. 1997 Dec 01; 100(11):2915-22. View in: Pubmed

      • Three-dimensional structure of the tyrosine kinase c-Src. Nature. 1997 Feb 13; 385(6617):595-602. View in: Pubmed

      • Analysis of the physical properties and molecular modeling of Sec13: A WD repeat protein involved in vesicular traffic. Biochemistry. 1996 Dec 03; 35(48):15215-21. View in: Pubmed

      • Phosphorylated T cell receptor zeta-chain and ZAP70 tandem SH2 domains form a 1:3 complex in vitro. Eur J Biochem. 1996 Jun 01; 238(2):440-5. View in: Pubmed

      • Structure of the IRS-1 PTB domain bound to the juxtamembrane region of the insulin receptor. Cell. 1996 May 31; 85(5):695-705. View in: Pubmed

      • Crystal structure of the PI 3-kinase p85 amino-terminal SH2 domain and its phosphopeptide complexes. Nat Struct Biol. 1996 Apr; 3(4):364-74. View in: Pubmed

      • Spatial constraints on the recognition of phosphoproteins by the tandem SH2 domains of the phosphatase SH-PTP2. Nature. 1996 Jan 18; 379(6562):277-80. View in: Pubmed

      • A new flavor in phosphotyrosine recognition. Structure. 1995 May 15; 3(5):421-4. View in: Pubmed

      • SH3 domains. Minding your p's and q's. Curr Biol. 1995 Apr 01; 5(4):364-7. View in: Pubmed

      • Catalytic specificity of protein-tyrosine kinases is critical for selective signalling. Nature. 1995 Feb 09; 373(6514):536-9. View in: Pubmed

      • Two crystal forms of the extracellular domain of type I tumor necrosis factor receptor. J Mol Biol. 1994 Jun 03; 239(2):332-5. View in: Pubmed

      • Role of acidic amino acids in the allosteric modulation by gallamine of antagonist binding at the m2 muscarinic acetylcholine receptor. Mol Pharmacol. 1994 May; 45(5):983-90. View in: Pubmed

      • Structure of the regulatory domains of the Src-family tyrosine kinase Lck. Nature. 1994 Apr 21; 368(6473):764-9. View in: Pubmed

      • Recognition of a high-affinity phosphotyrosyl peptide by the Src homology-2 domain of p56lck. Nature. 1993 Mar 04; 362(6415):87-91. View in: Pubmed

      • The structure of human lymphotoxin (tumor necrosis factor-beta) at 1.9-A resolution. J Biol Chem. 1992 Feb 05; 267(4):2119-22. View in: Pubmed

      • The structure of tumor necrosis factor-alpha at 2.6 A resolution. Implications for receptor binding. J Biol Chem. 1989 Oct 15; 264(29):17595-605. View in: Pubmed

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