Now showing items 1-9 of 9

    • Colon cancer-derived oncogenic EGFR G724S mutant identified by whole genome sequence analysis is dependent on asymmetric dimerization and sensitive to cetuximab 

      Cho, Jeonghee; Bass, Adam J; Lawrence, Michael S; Cibulskis, Kristian; Cho, Ahye; Lee, Shi-Nai; Yamauchi, Mai; Wagle, Nikhil; Pochanard, Panisa; Kim, Nayoung; Park, Angela KJ; Won, Jonghwa; Hur, Hyung-Suk; Greulich, Heidi; Ogino, Shuji; Sougnez, Carrie; Voet, Douglas; Tabernero, Josep; Jimenez, Jose; Baselga, Jose; Gabriel, Stacey B; Lander, Eric S; Getz, Gad; Eck, Michael J; Park, Woong-Yang; Meyerson, Matthew (BioMed Central, 2014)
      Background: Inhibition of the activated epidermal growth factor receptor (EGFR) with either enzymatic kinase inhibitors or anti-EGFR antibodies such as cetuximab, is an effective modality of treatment for multiple human ...
    • Crystal Structure of the FERM-SH2 Module of Human Jak2 

      McNally, Randall; Toms, Angela V.; Eck, Michael J. (Public Library of Science, 2016)
      Jak-family tyrosine kinases mediate signaling from diverse cytokine receptors. Binding of Jaks to their cognate receptors is mediated by their N-terminal region, which contains FERM and SH2 domains. Here we describe the ...
    • Crystal Structures of the FAK Kinase in Complex with TAE226 and Related Bis-Anilino Pyrimidine Inhibitors Reveal a Helical DFG Conformation 

      Lietha, Daniel; Eck, Michael Joseph (Public Library of Science, 2008)
      Focal Adhesion Kinase (FAK) is a non-receptor tyrosine kinase required for cell migration, proliferation and survival. FAK overexpression has been documented in diverse human cancers and is associated with a poor clinical ...
    • Genetic resistance to JAK2 enzymatic inhibitors is overcome by HSP90 inhibition 

      Weigert, Oliver; Bird, Liat; Kopp, Nadja; van Bodegom, Diederik; Marubayashi, Sachie; Christie, Amanda L.; Paranal, Ronald M.; Gaul, Christoph; Vangrevelinghe, Eric; Romanet, Vincent; Murakami, Masato; Tiedt, Ralph; Ebel, Nicolas; Evrot, Emeline; De Pover, Alain; Régnier, Catherine H.; Erdmann, Dirk; Hofmann, Francesco; Levine, Ross L.; Baffert, Fabienne; Radimerski, Thomas; Lane, Andrew Alan; Chapuy, Bjoern; Toms, Angela Vivian; McKeown, Michael Robert; Bradner, James Elliott; Yoda, Akinori; Eck, Michael Joseph; Sallan, Stephen Earl; Kung, Andrew; Weinstock, David Marc (The Rockefeller University Press, 2012)
      Enzymatic inhibitors of Janus kinase 2 (JAK2) are in clinical development for the treatment of myeloproliferative neoplasms (MPNs), B cell acute lymphoblastic leukemia (B-ALL) with rearrangements of the cytokine receptor ...
    • MELK is an oncogenic kinase essential for mitotic progression in basal-like breast cancer cells 

      Wang, Yubao; Lee, Young-Mi; Baitsch, Lukas; Huang, Alan; Xiang, Yi; Tong, Haoxuan; Lako, Ana; Von, Thanh; Choi, Christine; Lim, Elgene; Min, Junxia; Li, Li; Stegmeier, Frank; Schlegel, Robert; Eck, Michael J; Gray, Nathanael S; Mitchison, Timothy J; Zhao, Jean J (eLife Sciences Publications, Ltd, 2014)
      Despite marked advances in breast cancer therapy, basal-like breast cancer (BBC), an aggressive subtype of breast cancer usually lacking estrogen and progesterone receptors, remains difficult to treat. In this study, we ...
    • Overcoming EGFR T790M and C797S resistance with mutant-selective allosteric inhibitors 

      Jia, Yong; Yun, Cai-Hong; Park, Eunyoung; Ercan, Dalia; Manuia, Mari; Juarez, Jose; Xu, Chunxiao; Rhee, Kevin; Chen, Ting; Zhang, Haikuo; Palakurthi, Sangeetha; Jang, Jaebong; Lelais, Gerald; DiDonato, Michael; Bursulaya, Badry; Michellys, Pierre-Yves; Epple, Robert; Marsilje, Thomas H.; McNeill, Matthew; Lu, Wenshuo; Harris, Jennifer; Bender, Steven; Wong, Kwok-Kin; Jänne, Pasi A.; Eck, Michael J. (2016)
      EGFR tyrosine kinase inhibitors (TKIs) gefitinib, erlotinib and afatinib are approved treatments for non-small cell lung cancers harboring activating mutations in the EGFR kinase1,2, but resistance arises rapidly, most ...
    • Phosphorylated T Cell Receptor ζ-Chain and ZAP70 Tandem SH2 Domains Form a 1:3 Complex In Vitro 

      Weissenhorn, Winfried; Eck, Michael; Harrison, Stephen C.; Wiley, Don C. (Blackwell Science on behalf of the Federation of European Biochemical Societies, 1996)
      The ζ polypeptide is part of the T cell antigen receptor (TCR). The ζ-chain contributes to efficient cell-surface expression of the TCR and accounts for part of its signal transduction capability. TCR recognition triggers ...
    • Structure and mechanism of activity-based inhibition of the EGF-Receptor by Mig6 

      Park, Eunyoung; Kim, Nayoung; Ficarro, Scott B.; Zhang, Yi; Lee, Byung Il; Cho, Ahye; Kim, Kihong; Park, Angela K.J.; Park, Woong-Yang; Murray, Bradley; Meyerson, Matthew; Beroukhim, Rameen; Marto, Jarrod A.; Cho, Jeonghee; Eck, Michael J. (2016)
      Mig6 is a feedback inhibitor that directly binds, inhibits and drives internalization of ErbB-family receptors. Mig6 selectivity targets activated receptors. Here we find that the EGF receptor phosphorylates Mig6 on Tyr394, ...
    • Structure of a pseudokinase domain switch that controls oncogenic activation of Jak kinases 

      Toms, Angela V.; Deshpande, Anagha; McNally, Randall; Jeong, Youngjee; Rogers, Julia M.; Kim, Chae Un; Gruner, Sol M.; Ficarro, Scott B.; Marto, Jarrod A.; Sattler, Martin; Griffin, James D.; Eck, Michael J. (2013)
      The V617F mutation in the Jak2 pseudokinase domain causes myeloproliferative neoplasms, and the equivalent mutation in Jak1 (V658F) is found in T-cell leukemias. Crystal structures of wild type and V658F mutant human Jak1 ...