Stevan R Hubbard

Summary

Affiliation: New York University
Country: USA

Publications

  1. pmc The cytoplasmic adaptor protein Dok7 activates the receptor tyrosine kinase MuSK via dimerization
    Elisa Bergamin
    Structural Biology Program, Kimmel Center for Biology and Medicine of the Skirball Institute and Department of Pharmacology, New York University School of Medicine, New York, NY 10016, USA
    Mol Cell 39:100-9. 2010
  2. ncbi request reprint Structural basis for phosphotyrosine recognition by the Src homology-2 domains of the adapter proteins SH2-B and APS
    Junjie Hu
    Structural Biology Program, Skirball Institute of Biomolecular Medicine, and Department of Pharmacology, New York University School of Medicine, NY 10016, USA
    J Mol Biol 361:69-79. 2006
  3. ncbi request reprint Autoinhibitory mechanisms in receptor tyrosine kinases
    Stevan R Hubbard
    Skirball Institute of Biomolecular Medicine and Department of Pharmacology, New York University School of Medicine, New York, NY 10016, USA
    Front Biosci 7:d330-40. 2002
  4. pmc Receptor tyrosine kinases: mechanisms of activation and signaling
    Stevan R Hubbard
    Skirball Institute of Biomolecular Medicine and Department of Pharmacology, New York University School of Medicine, New York, NY 10016, USA
    Curr Opin Cell Biol 19:117-23. 2007
  5. ncbi request reprint Protein tyrosine kinases: autoregulation and small-molecule inhibition
    Stevan R Hubbard
    Skirball Institute of Biomolecular Medicine and Department of Pharmacology, New York University School of Medicine, New York 10016, USA
    Curr Opin Struct Biol 12:735-41. 2002
  6. ncbi request reprint EGF receptor inhibition: attacks on multiple fronts
    Stevan R Hubbard
    Structural Biology Program, Skirball Institute of Biomolecular Medicine, New York University School of Medicine, New York, New York 10016, USA
    Cancer Cell 7:287-8. 2005
  7. ncbi request reprint Juxtamembrane autoinhibition in receptor tyrosine kinases
    Stevan R Hubbard
    Skirball Institute of Biomolecular Medicine and Department of Pharmacology, New York University School of Medicine, New York 10016, USA
    Nat Rev Mol Cell Biol 5:464-71. 2004
  8. pmc Structural and functional studies of the Ras-associating and pleckstrin-homology domains of Grb10 and Grb14
    Rafael S Depetris
    Structural Biology Program, Kimmel Center for Biology and Medicine of the Skirball Institute, and Department of Pharmacology, New York University School of Medicine, New York, New York, USA
    Nat Struct Mol Biol 16:833-9. 2009
  9. ncbi request reprint Structural characterization of a novel Cbl phosphotyrosine recognition motif in the APS family of adapter proteins
    Junjie Hu
    Structural Biology Program, Skirball Institute of Biomolecular Medicine and Department of Pharmacology, New York University School of Medicine, New York, New York 10016, USA
    J Biol Chem 280:18943-9. 2005
  10. doi request reprint Structural and biochemical characterization of the KRLB region in insulin receptor substrate-2
    Jinhua Wu
    Structural Biology Program, Kimmel Center for Biology and Medicine of the Skirball Institute, and Department of Pharmacology, New York University School of Medicine, 540 First Avenue, New York, New York 10016, USA
    Nat Struct Mol Biol 15:251-8. 2008

Collaborators

Detail Information

Publications40

  1. pmc The cytoplasmic adaptor protein Dok7 activates the receptor tyrosine kinase MuSK via dimerization
    Elisa Bergamin
    Structural Biology Program, Kimmel Center for Biology and Medicine of the Skirball Institute and Department of Pharmacology, New York University School of Medicine, New York, NY 10016, USA
    Mol Cell 39:100-9. 2010
    ..The structure provides the molecular basis for MuSK activation by Dok7 and for rationalizing several Dok7 loss-of-function mutations found in patients with congenital myasthenic syndromes...
  2. ncbi request reprint Structural basis for phosphotyrosine recognition by the Src homology-2 domains of the adapter proteins SH2-B and APS
    Junjie Hu
    Structural Biology Program, Skirball Institute of Biomolecular Medicine, and Department of Pharmacology, New York University School of Medicine, NY 10016, USA
    J Mol Biol 361:69-79. 2006
    ..This differential specificity is attributable to the difference in the oligomeric states of the two SH2 domains: monomeric for SH2-B and dimeric for APS...
  3. ncbi request reprint Autoinhibitory mechanisms in receptor tyrosine kinases
    Stevan R Hubbard
    Skirball Institute of Biomolecular Medicine and Department of Pharmacology, New York University School of Medicine, New York, NY 10016, USA
    Front Biosci 7:d330-40. 2002
    ..This review will focus on the autoinhibitory mechanisms that modulate RTK catalytic activity...
  4. pmc Receptor tyrosine kinases: mechanisms of activation and signaling
    Stevan R Hubbard
    Skirball Institute of Biomolecular Medicine and Department of Pharmacology, New York University School of Medicine, New York, NY 10016, USA
    Curr Opin Cell Biol 19:117-23. 2007
    ....
  5. ncbi request reprint Protein tyrosine kinases: autoregulation and small-molecule inhibition
    Stevan R Hubbard
    Skirball Institute of Biomolecular Medicine and Department of Pharmacology, New York University School of Medicine, New York 10016, USA
    Curr Opin Struct Biol 12:735-41. 2002
    ....
  6. ncbi request reprint EGF receptor inhibition: attacks on multiple fronts
    Stevan R Hubbard
    Structural Biology Program, Skirball Institute of Biomolecular Medicine, New York University School of Medicine, New York, New York 10016, USA
    Cancer Cell 7:287-8. 2005
    ..Cetuximab targets one of the ligand binding domains of EGFR, thus preventing ligand activation of the receptor...
  7. ncbi request reprint Juxtamembrane autoinhibition in receptor tyrosine kinases
    Stevan R Hubbard
    Skirball Institute of Biomolecular Medicine and Department of Pharmacology, New York University School of Medicine, New York 10016, USA
    Nat Rev Mol Cell Biol 5:464-71. 2004
  8. pmc Structural and functional studies of the Ras-associating and pleckstrin-homology domains of Grb10 and Grb14
    Rafael S Depetris
    Structural Biology Program, Kimmel Center for Biology and Medicine of the Skirball Institute, and Department of Pharmacology, New York University School of Medicine, New York, New York, USA
    Nat Struct Mol Biol 16:833-9. 2009
    ....
  9. ncbi request reprint Structural characterization of a novel Cbl phosphotyrosine recognition motif in the APS family of adapter proteins
    Junjie Hu
    Structural Biology Program, Skirball Institute of Biomolecular Medicine and Department of Pharmacology, New York University School of Medicine, New York, New York 10016, USA
    J Biol Chem 280:18943-9. 2005
    ..These studies reveal a novel mode of phosphopeptide interaction with the Cbl TKB domain, in which N-terminal residues distal to the phosphotyrosine directly contact residues of the four-helix bundle of the TKB domain...
  10. doi request reprint Structural and biochemical characterization of the KRLB region in insulin receptor substrate-2
    Jinhua Wu
    Structural Biology Program, Kimmel Center for Biology and Medicine of the Skirball Institute, and Department of Pharmacology, New York University School of Medicine, 540 First Avenue, New York, New York 10016, USA
    Nat Struct Mol Biol 15:251-8. 2008
    ..Although Tyr628 was phosphorylated by the insulin receptor, its catalytic turnover was poor, resulting in kinase inhibition. Our studies indicate that the KRLB region functions to limit tyrosine phosphorylation of IRS2...
  11. ncbi request reprint Structural basis for recruitment of the adaptor protein APS to the activated insulin receptor
    Junjie Hu
    Skirball Institute of Biomolecular Medicine and Department of Pharmacology, New York University School of Medicine, New York, NY 10016, USA
    Mol Cell 12:1379-89. 2003
    ..This structure provides a molecular visualization of one of the initial downstream recruitment events following insulin activation of its dimeric receptor...
  12. ncbi request reprint Structural basis for inhibition of the insulin receptor by the adaptor protein Grb14
    Rafael S Depetris
    Structural Biology Program, Skirball Institute of Biomolecular Medicine and Department of Pharmacology, New York University School of Medicine, New York, New York 10016, USA
    Mol Cell 20:325-33. 2005
    ..Together with the crystal structure of the SH2 domain, we present a model for the interaction of Grb14 with the insulin receptor, which indicates how Grb14 functions as a selective protein inhibitor of insulin signaling...
  13. pmc Crystal structure of the frizzled-like cysteine-rich domain of the receptor tyrosine kinase MuSK
    Amy L Stiegler
    Structural Biology Program, Kimmel Center for Biology and Medicine of the Skirball Institute, New York University School of Medicine, New York, NY 10016, USA
    J Mol Biol 393:1-9. 2009
    ..An asymmetric dimer present in the crystal structure implicates surface hydrophobic residues that may function in homotypic or heterotypic interactions to mediate co-clustering of MuSK, rapsyn, and acetylcholine receptors at the NMJ...
  14. ncbi request reprint Structural and biochemical evidence for an autoinhibitory role for tyrosine 984 in the juxtamembrane region of the insulin receptor
    Shiqing Li
    Skirball Institute of Biomolecular Medicine and Department of Pharmacology, New York University School of Medicine, New York, New York 10016, USA
    J Biol Chem 278:26007-14. 2003
    ..In addition, the structural studies suggest a possible target site for small molecule activators of the insulin receptor, with potential use in the treatment of noninsulin-dependent diabetes mellitus...
  15. pmc Agrin binds to the N-terminal region of Lrp4 protein and stimulates association between Lrp4 and the first immunoglobulin-like domain in muscle-specific kinase (MuSK)
    Wei Zhang
    Molecular Neurobiology Program, Helen L and Martin S Kimmel Center for Biology and Medicine at the Skirball Institute of Biomolecular Medicine, New York University Medical School, New York, New York 10016, USA
    J Biol Chem 286:40624-30. 2011
    ..These findings suggest that Lrp4 is a cis-acting ligand for MuSK, whereas Agrin functions as an allosteric and paracrine regulator to promote association between Lrp4 and MuSK...
  16. pmc Mycobacterium tuberculosis prokaryotic ubiquitin-like protein-deconjugating enzyme is an unusual aspartate amidase
    Kristin E Burns
    Department of Microbiology, New York University, New York, New York 10016, USA
    J Biol Chem 287:37522-9. 2012
    ..We identified an aspartate as a potential nucleophile in the active site of Dop, suggesting a novel protease activity to target for inhibitor development...
  17. ncbi request reprint EGF receptor activation: push comes to shove
    Stevan R Hubbard
    Structural Biology Program, Skirball Institute of Biomolecular Medicine, and Department of Pharmacology, New York University School of Medicine, New York, NY 10016, USA
    Cell 125:1029-31. 2006
    ....
  18. pmc Small-molecule inhibition and activation-loop trans-phosphorylation of the IGF1 receptor
    Jinhua Wu
    Structural Biology Program, Kimmel Center for Biology and Medicine of the Skirball Institute of Biomolecular Medicine, Department of Pharmacology, New York University School of Medicine, New York, NY 10016, USA
    EMBO J 27:1985-94. 2008
    ....
  19. ncbi request reprint Structural basis for dimerization of the Grb10 Src homology 2 domain. Implications for ligand specificity
    Evan G Stein
    Skirball Institute of Biomolecular Medicine and Department of Pharmacology, New York University School of Medicine, New York, New York 10016, USA
    J Biol Chem 278:13257-64. 2003
    ..Moreover, the structure suggests the mechanism by which the Grb7 SH2 domain binds selectively to pTyr-1139 (pYVNQ) in Her2, which along with Grb7 is co-amplified in human breast cancers...
  20. ncbi request reprint Crystal structure of a complex between protein tyrosine phosphatase 1B and the insulin receptor tyrosine kinase
    Shiqing Li
    Structural Biology Program, Skirball Institute of Biomolecular Medicine and Department of Pharmacology, New York University School of Medicine, New York, New York 10016, USA
    Structure 13:1643-51. 2005
    ..The crystal structure provides evidence for a noncatalytic mode of interaction between PTP1B and IRK, which could be important for the selective recruitment of PTP1B to the insulin receptor...
  21. pmc Crystal structure of the agrin-responsive immunoglobulin-like domains 1 and 2 of the receptor tyrosine kinase MuSK
    Amy L Stiegler
    Structural Biology Program, Skirball Institute of Biomolecular Medicine and Department of Pharmacology, New York University School of Medicine, New York, NY 10016, USA
    J Mol Biol 364:424-33. 2006
    ..Biochemical analyses of MuSK mutants introduced into MuSK(-/-) myotubes demonstrate that residues in this hydrophobic patch are critical for agrin-induced MuSK activation...
  22. pmc Lrp4 is a receptor for Agrin and forms a complex with MuSK
    Natalie Kim
    Molecular Neurobiology Program, Skirball Institute of Biomolecular Medicine, Helen and Martin Kimmel Center for Biology and Medicine, NYU Medical School, New York, NY 10016, USA
    Cell 135:334-42. 2008
    ..Here, we report that Lrp4, a member of the LDLR family, is a receptor for Agrin, forms a complex with MuSK, and mediates MuSK activation by Agrin...
  23. ncbi request reprint Molecular basis for pseudokinase-dependent autoinhibition of JAK2 tyrosine kinase
    Yibing Shan
    1 D E Shaw Research, New York, New York, USA 2
    Nat Struct Mol Biol 21:579-84. 2014
    ..The simulations indicate that the kinase domain is stabilized in an inactive state by the pseudokinase domain, and they offer a molecular rationale for the hyperactivity of V617F, the predominant JAK2 MPN mutation. ..
  24. pmc Crystal structures of the JAK2 pseudokinase domain and the pathogenic mutant V617F
    Rajintha M Bandaranayake
    Structural Biology Program, Kimmel Center for Biology and Medicine at the Skirball Institute, New York University School of Medicine, New York, New York, USA
    Nat Struct Mol Biol 19:754-9. 2012
    ..The crystal structures of JH2 afford new opportunities for the design of novel JAK2 therapeutics targeting MPNs...
  25. ncbi request reprint Crystal structure of the human laminin receptor precursor
    Kelly V Jamieson
    Gene Therapy Center, Cancer Institute and Department of Pathology, New York University School of Medicine, New York, New York 10016, USA
    J Biol Chem 283:3002-5. 2008
    ..Here, we report the crystal structure of human LamR, which provides insights into its function and should facilitate the design of novel therapeutics targeting LamR...
  26. pmc Structure and activation of MuSK, a receptor tyrosine kinase central to neuromuscular junction formation
    Stevan R Hubbard
    Kimmel Center for Biology and Medicine of the Skirball Institute, New York University School of Medicine, New York, NY 10016, USA Department of Biochemistry and Molecular Pharmacology, New York University School of Medicine, New York, NY 10016, USA Electronic address
    Biochim Biophys Acta 1834:2166-9. 2013
    ..This article is part of a Special Issue entitled: Emerging recognition and activation mechanisms of receptor tyrosine kinases. ..
  27. ncbi request reprint Structural basis for phosphotyrosine recognition by suppressor of cytokine signaling-3
    Elisa Bergamin
    Structural Biology Program, Skirball Institute of Biomolecular Medicine and Department of Pharmacology, New York University School of Medicine, New York, New York 10016, USA
    Structure 14:1285-92. 2006
    ..In addition, the structure provides insights into the possible mechanisms by which SOCS3 and SOCS1 inhibit JAK2 kinase activity...
  28. ncbi request reprint Cytokine signaling exposed
    Stevan R Hubbard
    Structural Biology Program, Kimmel Center for Biology and Medicine of the Skirball Institute, New York University School of Medicine, New York, NY 10016, USA
    Structure 19:1-2. 2011
    ....
  29. pmc Structural basis for the interaction of the adaptor protein grb14 with activated ras
    Rohini Qamra
    Kimmel Center for Biology and Medicine of the Skirball Institute and Department of Biochemistry and Molecular Pharmacology, New York University School of Medicine, New York, NY, USA
    PLoS ONE 8:e72473. 2013
    ..The structure of Grb14 RA-PH in complex with H-Ras represents the first detailed molecular characterization of tandem RA-PH domains bound to a small GTPase and provides insights into the molecular basis for specificity. ..
  30. pmc The insulin receptor: both a prototypical and atypical receptor tyrosine kinase
    Stevan R Hubbard
    Kimmel Center for Biology and Medicine of the Skirball Institute and Department of Biochemistry and Molecular Pharmacology, New York University School of Medicine, New York, New York 10016, USA
    Cold Spring Harb Perspect Biol 5:a008946. 2013
    ....
  31. pmc Rap1-interacting adapter molecule (RIAM) associates with the plasma membrane via a proximity detector
    Joseph P Wynne
    Cancer Institute, NYU School of Medicine, New York, NY 10016, USA
    J Cell Biol 199:317-30. 2012
    ..Thus, the RA-PH domains of RIAM function as a proximity detector for activated Rap1 and PI(4,5)P(2)...
  32. pmc Structure-guided identification of a laminin binding site on the laminin receptor precursor
    Kelly V Jamieson
    Department of Pathology, New York University School of Medicine, New York, NY 10016, USA
    J Mol Biol 405:24-32. 2011
    ..Mapping of the LamR binding site should contribute to the development of therapeutics that inhibit LamR interactions with laminin and may aid in the prevention of tumor growth and metastasis...
  33. ncbi request reprint Crystal structure of the MuSK tyrosine kinase: insights into receptor autoregulation
    Jeffrey H Till
    Skirball Institute of Biomolecular Medicine and Department of Pharmacology, New York University School of Medicine, New York, NY 10016, USA
    Structure 10:1187-96. 2002
    ..These studies provide a molecular basis for understanding the regulation of MuSK catalytic activity and suggest that an additional in vivo component may contribute to regulation via the juxtamembrane region...
  34. ncbi request reprint The juxtamembrane region of EGFR takes center stage
    Stevan R Hubbard
    Structural Biology Program, Kimmel Center for Biology and Medicine of the Skirball Institute, New York University School of Medicine, New York, NY 10016, USA
    Cell 137:1181-3. 2009
    ..Jura et al. (2009) in this issue and Brewer et al. (2009) in Molecular Cell now demonstrate that the juxtamembrane region of EGFR plays a crucial role in stabilizing this dimer...
  35. doi request reprint How IRE1 reacts to ER stress
    David Ron
    Kimmel Center for Biology and Medicine of the Skirball Institute, New York University School of Medicine, New York, NY 10016, USA
    Cell 132:24-6. 2008
    ..2008). This structure provides new insight into the mysterious coupling of kinase and endoribonuclease activities in the oldest, most-conserved branch of the unfolded protein response in eukaryotes...
  36. ncbi request reprint Oncogenic mutations in B-Raf: some losses yield gains
    Stevan R Hubbard
    Skirball Institute of Biomolecular Medicine and Department of Pharmacology, New York University School of Medicine, New York, NY 10016, USA
    Cell 116:764-6. 2004
    ..Surprisingly, several mutations lead to impaired B-Raf kinase activity, yet these mutants are nevertheless capable of stimulating downstream signaling through transactivation of C-Raf...
  37. pmc Molecular analysis of the prokaryotic ubiquitin-like protein (Pup) conjugation pathway in Mycobacterium tuberculosis
    Francisca A Cerda-Maira
    New York University School of Medicine, Department of Microbiology, 550 First Avenue, New York, NY 10016, USA
    Mol Microbiol 77:1123-35. 2010
    ..Finally, using structural models and site-directed mutagenesis our data suggest that Dop and PafA are members of the glutamine synthetase fold family of proteins...
  38. ncbi request reprint IRE1 couples endoplasmic reticulum load to secretory capacity by processing the XBP-1 mRNA
    Marcella Calfon
    Skirball Institute of Biomolecular Medicine, New York University School of Medicine, New York, NY 10016, USA
    Nature 415:92-6. 2002
    ..Our findings suggest that physiological ER load regulates a developmental decision in higher eukaryotes...
  39. ncbi request reprint Agrin/MuSK signaling: willing and Abl
    Steven J Burden
    Nat Neurosci 6:653-4. 2003
  40. ncbi request reprint Bisubstrate analog probes for the insulin receptor protein tyrosine kinase: molecular yardsticks for analyzing catalytic mechanism and inhibitor design
    Aliya C Hines
    Department of Pharmacology and Molecular Sciences, Johns Hopkins University School of Medicine, Baltimore, MD 21205, USA
    Bioorg Chem 33:285-97. 2005
    ..Taken together, these results suggest that a combination of mechanism-based design and empirical synthetic manipulation will be necessary in producing optimized protein kinase bisubstrate analog inhibitors...