Joseph Avruch

Summary

Affiliation: Harvard University
Country: USA

Publications

  1. pmc Protein kinases of the Hippo pathway: regulation and substrates
    Joseph Avruch
    Department of Molecular Biology, Massachusetts General Hospital, Boston, MA 02114, USA
    Semin Cell Dev Biol 23:770-84. 2012
  2. pmc YAP oncogene overexpression supercharges colon cancer proliferation
    Joseph Avruch
    Department of Molecular Biology, Massachusetts General Hospital, Boston, MA, USA
    Cell Cycle 11:1090-6. 2012
  3. ncbi request reprint Insulin and amino-acid regulation of mTOR signaling and kinase activity through the Rheb GTPase
    J Avruch
    Diabetes Research Lab, Department of Molecular Biology, Massachusetts General Hospital, Boston, MA 02114, USA
    Oncogene 25:6361-72. 2006
  4. pmc Amino acid regulation of TOR complex 1
    Joseph Avruch
    Department of Molecular Biology and Diabetes Research Unit, Medical Service, Massachusetts General Hospital, and Department of Medicine, Harvard Medical School, Simches Research Center, Boston, MA 02114, USA
    Am J Physiol Endocrinol Metab 296:E592-602. 2009
  5. pmc Rassf family of tumor suppressor polypeptides
    Joseph Avruch
    Department of Molecular Biology, Massachusetts General Hospital, Boston, MA, USA
    J Biol Chem 284:11001-5. 2009
  6. doi request reprint Activation of mTORC1 in two steps: Rheb-GTP activation of catalytic function and increased binding of substrates to raptor
    Joseph Avruch
    Diabetes Research Laboratory, Department of Molecular Biology, Diabetes Unit, Medical Services, Massachusetts General Hospital, Simches Research Building, 6408, 185 Cambridge Street, Boston, MA 02114, USA
    Biochem Soc Trans 37:223-6. 2009
  7. pmc MAP kinase pathways: the first twenty years
    Joseph Avruch
    Department of Molecular Biology and the Diabetes Unit, Medical Services, Massachusetts General Hospital, and Department of Medicine, Harvard Medical School, 185 Cambridge St, Boston, MA 02114 2790, USA
    Biochim Biophys Acta 1773:1150-60. 2007
  8. pmc Mst1/2 signalling to Yap: gatekeeper for liver size and tumour development
    J Avruch
    Department of Molecular Biology, Massachusetts General Hospital, Simches Research Building, 6408, 185 Cambridge Street, Boston, MA 02115, USA
    Br J Cancer 104:24-32. 2011
  9. ncbi request reprint Rheb binds and regulates the mTOR kinase
    Xiaomeng Long
    Diabetes Unit and Medical Services and Department of Molecular Biology, Massachusetts General Hospital, Boston, 02114, USA
    Curr Biol 15:702-13. 2005
  10. pmc The mechanism of insulin-stimulated 4E-BP protein binding to mammalian target of rapamycin (mTOR) complex 1 and its contribution to mTOR complex 1 signaling
    Joseph Rapley
    Department of Molecular Biology and Diabetes Unit of the Medical Services, Massachusetts General Hospital, Harvard Medical School, Boston, Massachusetts 02114, USA
    J Biol Chem 286:38043-53. 2011

Collaborators

Detail Information

Publications66

  1. pmc Protein kinases of the Hippo pathway: regulation and substrates
    Joseph Avruch
    Department of Molecular Biology, Massachusetts General Hospital, Boston, MA 02114, USA
    Semin Cell Dev Biol 23:770-84. 2012
    ....
  2. pmc YAP oncogene overexpression supercharges colon cancer proliferation
    Joseph Avruch
    Department of Molecular Biology, Massachusetts General Hospital, Boston, MA, USA
    Cell Cycle 11:1090-6. 2012
    ..This interplay between overexpressed YAP and β-catenin also drives proliferation of colon cancer cells. The dispensability of YAP in normal intestine makes YAP's expression or outputs attractive targets for cancer therapy...
  3. ncbi request reprint Insulin and amino-acid regulation of mTOR signaling and kinase activity through the Rheb GTPase
    J Avruch
    Diabetes Research Lab, Department of Molecular Biology, Massachusetts General Hospital, Boston, MA 02114, USA
    Oncogene 25:6361-72. 2006
    ..The components of the insulin/IGF pathway to TORC1 are now well established, whereas the elements mediating the more ancient and functionally dominant input of amino acids remain largely unknown...
  4. pmc Amino acid regulation of TOR complex 1
    Joseph Avruch
    Department of Molecular Biology and Diabetes Research Unit, Medical Service, Massachusetts General Hospital, and Department of Medicine, Harvard Medical School, Simches Research Center, Boston, MA 02114, USA
    Am J Physiol Endocrinol Metab 296:E592-602. 2009
    ..The type III phosphatidylinositol kinase also participates in amino acid-dependent mTORC1 activation, although the site of action of its product, 3'OH-phosphatidylinositol, in this process is unclear...
  5. pmc Rassf family of tumor suppressor polypeptides
    Joseph Avruch
    Department of Molecular Biology, Massachusetts General Hospital, Boston, MA, USA
    J Biol Chem 284:11001-5. 2009
    ..Herein, we review the binding of the Rassf polypeptides to Ras-like GTPases and the Mst1/2 kinases and their role in Rassf function...
  6. doi request reprint Activation of mTORC1 in two steps: Rheb-GTP activation of catalytic function and increased binding of substrates to raptor
    Joseph Avruch
    Diabetes Research Laboratory, Department of Molecular Biology, Diabetes Unit, Medical Services, Massachusetts General Hospital, Simches Research Building, 6408, 185 Cambridge Street, Boston, MA 02114, USA
    Biochem Soc Trans 37:223-6. 2009
    ..The mechanism underlying this second step in the activation of mTORC1 is unknown...
  7. pmc MAP kinase pathways: the first twenty years
    Joseph Avruch
    Department of Molecular Biology and the Diabetes Unit, Medical Services, Massachusetts General Hospital, and Department of Medicine, Harvard Medical School, 185 Cambridge St, Boston, MA 02114 2790, USA
    Biochim Biophys Acta 1773:1150-60. 2007
    ..The discovery of these kinases is reviewed, followed by a discussion of some of the features of this signaling module that account for its broad impact on cell function and its enormous interest to many investigators...
  8. pmc Mst1/2 signalling to Yap: gatekeeper for liver size and tumour development
    J Avruch
    Department of Molecular Biology, Massachusetts General Hospital, Simches Research Building, 6408, 185 Cambridge Street, Boston, MA 02115, USA
    Br J Cancer 104:24-32. 2011
    ..In this review, we discuss the role of Hippo signalling in liver biology and the contribution of this pathway to liver cancer in humans...
  9. ncbi request reprint Rheb binds and regulates the mTOR kinase
    Xiaomeng Long
    Diabetes Unit and Medical Services and Department of Molecular Biology, Massachusetts General Hospital, Boston, 02114, USA
    Curr Biol 15:702-13. 2005
    ..The Tuberous Sclerosis heterodimer (TSC1/TSC2) functions as a Rheb GTPase activator and inhibits TOR signaling in vivo...
  10. pmc The mechanism of insulin-stimulated 4E-BP protein binding to mammalian target of rapamycin (mTOR) complex 1 and its contribution to mTOR complex 1 signaling
    Joseph Rapley
    Department of Molecular Biology and Diabetes Unit of the Medical Services, Massachusetts General Hospital, Harvard Medical School, Boston, Massachusetts 02114, USA
    J Biol Chem 286:38043-53. 2011
    ....
  11. ncbi request reprint Identification of a novel Ras-regulated proapoptotic pathway
    Andrei Khokhlatchev
    Diabetes Unit and Medical Services, Massachusetts General Hospital, Boston, MA 02114, USA
    Curr Biol 12:253-65. 2002
    ..NORE1, a noncatalytic polypeptide, binds specifically to Ras-GTP and to several other Ras-like GTPases. NORE is homologous to the putative tumor suppressor RASSF1 and to the Caenorhabditis elegans polypeptide T24F1.3...
  12. ncbi request reprint The scaffold protein CNK1 interacts with the tumor suppressor RASSF1A and augments RASSF1A-induced cell death
    Shahrooz Rabizadeh
    Department of Molecular Biology, Massachusetts General Hospital, Boston, Massachusetts 02114, USA
    J Biol Chem 279:29247-54. 2004
    ..Thus, in addition to its positive role in the proliferative outputs of active Ras, the CNK1 scaffold protein, through its binding of a RASSF1A.MST complex, also participates in the proapoptotic signaling initiated by active Ras...
  13. pmc Mst1 and Mst2 maintain hepatocyte quiescence and suppress hepatocellular carcinoma development through inactivation of the Yap1 oncogene
    Dawang Zhou
    Department of Molecular Biology, Massachusetts General Hospital, Boston, MA 02114, USA
    Cancer Cell 16:425-38. 2009
    ..Approximately 30% of human HCCs show low Yap1(Ser127) phosphorylation and a majority exhibit loss of cleaved, activated Mst1. Mst1/2 inhibition of Yap1 is an important pathway for tumor suppression in liver relevant to human HCC...
  14. doi request reprint MOBKL1A/MOBKL1B phosphorylation by MST1 and MST2 inhibits cell proliferation
    Maria Praskova
    Diabetes Unit and Medical Services and Department of Molecular Biology, Massachusetts General Hospital, Boston, Massachusetts 02114, USA
    Curr Biol 18:311-21. 2008
    ....
  15. pmc The Rheb switch 2 segment is critical for signaling to target of rapamycin complex 1
    Xiaomeng Long
    Diabetes Unit and Medical Services, Department of Molecular Biology, Massachusetts General Hospital, and Department of Medicine, Harvard Medical School, Boston 02114, USA
    J Biol Chem 282:18542-51. 2007
    ..We conclude that Rheb signaling to mTOR in vivo requires a Rheb switch 2-dependent interaction with an element other than the three known polypeptide components of TOR complex 1...
  16. doi request reprint The NIMA-family kinase Nek6 phosphorylates the kinesin Eg5 at a novel site necessary for mitotic spindle formation
    Joseph Rapley
    Department of Molecular Biology and Medical Services, Massachusetts General Hospital and Department of Medicine, Harvard Medical School, Boston, MA 02114, USA
    J Cell Sci 121:3912-21. 2008
    ..Thus, during mitosis Nek6 phosphorylates a subset of Eg5 polypeptides at a conserved site, the phosphorylation of which is crucial for the mitotic function of Eg5...
  17. pmc The Nore1B/Mst1 complex restrains antigen receptor-induced proliferation of naïve T cells
    Dawang Zhou
    Department of Molecular Biology, Massachusetts General Hospital, Boston, MA 02114, USA
    Proc Natl Acad Sci U S A 105:20321-6. 2008
    ..The Nore1B/RAPL-Mst1 complex is a negative regulator of naïve T cell proliferation...
  18. pmc The Mst1 and Mst2 kinases control activation of rho family GTPases and thymic egress of mature thymocytes
    Fan Mou
    Department of Molecular Biology, Massachusetts GeneralHospital, Boston, MA 02114, USA
    J Exp Med 209:741-59. 2012
    ..Thus, the Mst1 and Mst2 kinases control Rho GTPase activation and the migratory responses of SP thymocytes...
  19. ncbi request reprint Nore1 and RASSF1 regulation of cell proliferation and of the MST1/2 kinases
    Joseph Avruch
    Department of Molecular Biology and Diabetes Unit, Medical Services, Massachusetts General Hospital, USA
    Methods Enzymol 407:290-310. 2006
    ..At present, however, the relevance of Ki-Ras-induced apoptosis to the physiological functions of c-Ras and to the growth-regulating actions of spontaneously occurring oncogenic Ras mutants is not known...
  20. ncbi request reprint Rheb binding to mammalian target of rapamycin (mTOR) is regulated by amino acid sufficiency
    Xiaomeng Long
    Diabetes Unit and Medical Services and the Department of Molecular Biology, Massachusetts General Hospital, Boston 02114, USA
    J Biol Chem 280:23433-6. 2005
    ..Amino acid withdrawal may generate an inhibitor of the Rheb-mTOR interaction that interferes with the signaling function of TOR complex 1...
  21. pmc Regulation of the MST1 kinase by autophosphorylation, by the growth inhibitory proteins, RASSF1 and NORE1, and by Ras
    Maria Praskova
    Diabetes Unit and Medical Services and Department of Molecular Biology, Massachusetts General Hospital, Boston, MA 02114, USA
    Biochem J 381:453-62. 2004
    ..We propose that the NORE1/RASSF1 polypeptides, in addition to their role in maintaining the low activity of MST1 in vivo, direct MST1 to sites of activation and perhaps co-localization with endogenous substrates...
  22. doi request reprint Amino acids activate mammalian target of rapamycin (mTOR) complex 1 without changing Rag GTPase guanyl nucleotide charging
    Noriko Oshiro
    From the Department of Molecular Biology and Diabetes Unit, Medical Services, Massachusetts General Hospital, Boston, Massachusetts 02114 and the Department of Medicine, Harvard Medical School, Boston, Massachusetts 02115
    J Biol Chem 289:2658-74. 2014
    ..Thus, amino acids promote mTORC1 activation without altering Rag GTP charging. Raptor binding to Rag, although necessary, is not sufficient for mTORC1 activation. Additional amino acid-dependent steps couple Rag-mTORC1 to Rheb-GTP. ..
  23. doi request reprint G protein-coupled receptors engage the mammalian Hippo pathway through F-actin: F-Actin, assembled in response to Galpha12/13 induced RhoA-GTP, promotes dephosphorylation and activation of the YAP oncogene
    Laura Regué
    Department of Molecular Biology, Massachusetts General Hospital, Boston, MA, USA
    Bioessays 35:430-5. 2013
    ..These findings unveil the ability of GPCRs to activate the YAP oncogene through a newly recognized signaling function of the actin cytoskeleton, likely to be especially important for normal and cancerous stem cells...
  24. ncbi request reprint A mitotic cascade of NIMA family kinases. Nercc1/Nek9 activates the Nek6 and Nek7 kinases
    Christopher Belham
    Department of Molecular Biology and Medical Services, Massachusetts General Hospital, and Harvard Medical School, Boston, Massachusetts 02114, USA
    J Biol Chem 278:34897-909. 2003
    ..These findings support the conclusion that Nercc1/Nek9 and Nek6 represent a novel cascade of mitotic NIMA family protein kinases whose combined function is important for mitotic progression...
  25. pmc Mst1 and Mst2 protein kinases restrain intestinal stem cell proliferation and colonic tumorigenesis by inhibition of Yes-associated protein (Yap) overabundance
    Dawang Zhou
    Department of Molecular Biology, Harvard Medical School, Boston, MA 02115, USA
    Proc Natl Acad Sci U S A 108:E1312-20. 2011
    ..The dispensability of Yap1 in normal intestinal homeostasis and its potent proliferative and prosurvival actions when overexpressed in colon cancer make it an attractive therapeutic target...
  26. pmc A genome-wide RNAi screen for polypeptides that alter rpS6 phosphorylation
    Angela Papageorgiou
    Diabetes Unit and Medical Services and Department of Molecular Biology, Massachusetts General Hospital, Boston, MA, USA
    Methods Mol Biol 821:187-214. 2012
    ..Identifying previously unappreciated proteins needed for maintenance of mTORC1 activity may provide new targets and lead to the development of beneficial therapies for pancreatic cancer...
  27. ncbi request reprint Death-associated protein 4 binds MST1 and augments MST1-induced apoptosis
    Yenshou Lin
    Diabetes Unit, Massachusetts General Hospital, Boston 02114, USA
    J Biol Chem 277:47991-8001. 2002
    ..MST1 is unable to directly phosphorylate p53, however, DAP4 binds endogenous and recombinant p53. DAP4 may promote MST1-induced apoptosis by enabling colocalization of MST with p53...
  28. ncbi request reprint Nore1 inhibits tumor cell growth independent of Ras or the MST1/2 kinases
    Yumi Aoyama
    Diabetes Unit and Medical Services, Massachusetts General Hospital, Boston, MA 02114, USA
    Oncogene 23:3426-33. 2004
    ..Thus, Nore1 suppresses the growth of some tumor cell lines through as yet unidentified effectors, independent of Ras-like proteins or MST1/2...
  29. ncbi request reprint Recent advances in the regulation of the TOR pathway by insulin and nutrients
    Joseph Avruch
    Diabetes Unit and Medical Services and Department of Molecular Biology, Massachusetts General Hospital, Boston, Massachusetts, USA
    Curr Opin Clin Nutr Metab Care 8:67-72. 2005
    ....
  30. pmc Active Nercc1 protein kinase concentrates at centrosomes early in mitosis and is necessary for proper spindle assembly
    Joan Roig
    Department of Molecular Biology and Medical Services, Massachusetts General Hospital Harvard Medical School, Boston, MA 02114, USA
    Mol Biol Cell 16:4827-40. 2005
    ..Thus, Nercc1 contributes to both the centrosomal and the chromatin/Ran pathways that collaborate in the organization of a bipolar spindle...
  31. pmc mTOR complex 2 phosphorylates IMP1 cotranslationally to promote IGF2 production and the proliferation of mouse embryonic fibroblasts
    Ning Dai
    Department of Molecular Biology, Massachusetts General Hospital, Boston, MA 02114, USA
    Genes Dev 27:301-12. 2013
    ..Inasmuch as TORC2 is activated by association with ribosomes, the present results indicate that mTORC2-catalyzed cotranslational protein phosphorylation is a core function of this complex...
  32. ncbi request reprint TOR deficiency in C. elegans causes developmental arrest and intestinal atrophy by inhibition of mRNA translation
    Xiaomeng Long
    Department of Molecular Biology, Massachusetts General Hospital, Harvard Medical School, Boston 02114, USA
    Curr Biol 12:1448-61. 2002
    ..We describe a C. elegans TOR homolog (CeTOR) and phenotypes associated with CeTOR deficiency. These phenotypes are compared with the response to starvation and the inactivation of a variety of putative TOR targets...
  33. pmc Yap1 acts downstream of α-catenin to control epidermal proliferation
    Karin Schlegelmilch
    Stem Cell Program, Children s Hospital, Boston, MA 02115, USA
    Cell 144:782-95. 2011
    ..Together, these data identify Yap1 as a determinant of the proliferative capacity of epidermal stem cells and as an important effector of a "crowd control" molecular circuitry in mammalian skin...
  34. pmc mTOR phosphorylates IMP2 to promote IGF2 mRNA translation by internal ribosomal entry
    Ning Dai
    Department of Molecular Biology, Massachusetts General Hospital, Boston, USA
    Genes Dev 25:1159-72. 2011
    ..Doubly phosphorylated IMP2 is also widely expressed in adult tissues, including islets of Langerhans...
  35. ncbi request reprint Glutamatergic regulation of the p70S6 kinase in primary mouse neurons
    Guido Lenz
    Department of Molecular Biology and the Diabetes Unit and Medical Services, Massachusetts General Hospital, Boston, Massachusetts 02114, USA
    J Biol Chem 280:38121-4. 2005
    ....
  36. pmc Characterization of two Mst1-deficient mouse models
    Montserrat C Anguera
    Howard Hughes Medical Institute, Department of Molecular Biology, Massachusetts General Hospital, Department of Genetics, Harvard Medical School, Boston, Massachusetts 02114, USA
    Dev Dyn 237:3424-34. 2008
    ..Thus, a mutation in Mst1 alone does not affect survival. Our results set the stage for identification of the lethal second-site mutation that is paradoxically favored for transmission...
  37. ncbi request reprint The putative tumor suppressor RASSF1A homodimerizes and heterodimerizes with the Ras-GTP binding protein Nore1
    Sara Ortiz-Vega
    Diabetes Unit and Medical Services, Massachusetts General Hospital, Boston, Massachusetts, MA 02114, USA
    Oncogene 21:1381-90. 2002
    ..The preferential ability of RASSF1A to heterodimerize with Nore and thereby associate with Ras-like GTPases may be relevant to its putative tumor suppressor function...
  38. pmc Nercc1, a mammalian NIMA-family kinase, binds the Ran GTPase and regulates mitotic progression
    Joan Roig
    Department of Molecular Biology and the Diabetes Unit and Medical Services, Massachusetts General Hospital, and the Department of Medicine, Harvard Medical School, Boston, Massachusetts 02114, USA
    Genes Dev 16:1640-58. 2002
    ..Nercc1 and its partner Nek6 represent a new signaling pathway that regulates mitotic progression...
  39. ncbi request reprint Mammalian mitogen-activated protein kinase signal transduction pathways activated by stress and inflammation
    J M Kyriakis
    Diabetes Research Laboratory, Medical Services, Massachusetts General Hospital, Boston, Massachusetts 02129, USA
    Physiol Rev 81:807-69. 2001
    ..The nuclear factor-kappa B pathway, a second stress signaling paradigm, has been the subject of several excellent recent reviews (258, 260)...
  40. doi request reprint Mammalian MAPK signal transduction pathways activated by stress and inflammation: a 10-year update
    John M Kyriakis
    Molecular Cardiology Research Institute, Tufts Medical Center, 800 Washington St, Box 8486, Boston, MA 02111, USA
    Physiol Rev 92:689-737. 2012
    ..Herein we first summarize the molecular components of the mammalian stress-regulated MAPK pathways and their regulation as described thus far. We then review some of the in vivo functions of these pathways...
  41. ncbi request reprint Ionizing radiation stimulates a Grb2-mediated association of the stress-activated protein kinase with phosphatidylinositol 3-kinase
    S Kharbanda
    Division of Cancer Pharmacology, Dana Farber Cancer Institute, Boston, Massachusetts 02115, USA
    J Biol Chem 270:18871-4. 1995
    ..These results suggest that the cellular response to IR may include regulation of SAP kinase by a PI 3-kinase-dependent signaling pathway...
  42. pmc Molecular structure of a major insulin/mitogen-activated 70-kDa S6 protein kinase
    P Banerjee
    Diabetes Unit, Massachusetts General Hospital, Boston 02129
    Proc Natl Acad Sci U S A 87:8550-4. 1990
    ..Thus, hormonal regulation of S6 kinase may involve the action of MPF/cdc-2 or protein kinases with related substrate specificity...
  43. ncbi request reprint The stress-activated protein kinase subfamily of c-Jun kinases
    J M Kyriakis
    Diabetes Research Laboratory, Medical Services, Massachusetts General Hospital East, Charlestown 02129
    Nature 369:156-60. 1994
    ..9). SAPKs therefore define a new TNF-alpha and stress-activated signalling pathway, possibly initiated by sphingomyelin-based second messengers, which regulates the activity of c-Jun...
  44. ncbi request reprint Insulin-activated protein kinases phosphorylate a pseudosubstrate synthetic peptide inhibitor of the p70 S6 kinase
    D J Price
    Diabetes Unit, Massachusetts General Hospital, Boston 02129
    J Biol Chem 266:16281-4. 1991
    ..Thus, these sequences of p70 S6 kinase constitute a potential autoinhibitory pseudosubstrate site, whose phosphorylation is catalyzed by candidate upstream-activating protein kinases...
  45. pmc Cloning and expression of two human p70 S6 kinase polypeptides differing only at their amino termini
    J R Grove
    Medical Services, Massachusetts General Hospital, Boston
    Mol Cell Biol 11:5541-50. 1991
    ..Acquisition of S6 protein kinase catalytic function, however, is apparently restricted to the most extensively phosphorylated recombinant polypeptides...
  46. ncbi request reprint Identification of the NIMA family kinases NEK6/7 as regulators of the p70 ribosomal S6 kinase
    C Belham
    Diabetes Unit, Medical Services, Massachusetts General Hospital, Boston, MA 02114, USA
    Curr Biol 11:1155-67. 2001
    ..g.,Thr412 in p70 S6 kinase (alpha 1). Phosphorylation of the former site is catalyzed by PDK1, whereas the kinase responsible for the phosphorylation of the latter site is not known...
  47. ncbi request reprint TOR action in mammalian cells and in Caenorhabditis elegans
    X Long
    Diabetes Research Laboratory, Department of Molecular Biology, Land Medicine Massachusetts General Hospital, Boston, MA 02114, USA
    Curr Top Microbiol Immunol 279:115-38. 2004
    ..One pathway for RTK control involves the tuberous sclerosis complex, which is absent in C. elegans, but of major importance in Drosophila and higher metazoans...
  48. ncbi request reprint Regulation of eIF-4E BP1 phosphorylation by mTOR
    K Hara
    Diabetes Unit and Medical Services, Massachusetts General Hospital, and Harvard Medical School, Boston, Massachusetts 02129, USA
    J Biol Chem 272:26457-63. 1997
    ..We conclude that mTOR is an upstream regulator of eIF-4E BP1 as well as the p70 S6 kinase; moreover, these two mTOR targets are regulated in a parallel rather than sequential manner...
  49. ncbi request reprint Ras activation of the Raf kinase: tyrosine kinase recruitment of the MAP kinase cascade
    J Avruch
    Diabetes Unit and Medical Services, Massachusetts General Hospital, Boston 02114, USA
    Recent Prog Horm Res 56:127-55. 2001
    ..We will then review in more detail current understanding of the biochemical mechanism through which the Ras proto-oncogene, in collaboration with the 14-3-3 protein and other protein kinases, initiates activation of the Raf kinase...
  50. ncbi request reprint Characterization of ubiquilin 1, an mTOR-interacting protein
    Shilan Wu
    Department of Molecular Biology, Massachusetts General Hospital, Boston, MA 02135, USA
    Biochim Biophys Acta 1542:41-56. 2002
    ..Our data suggest that we have identified a novel mTOR interactor, ubiquilin 1. The biological significance of this, presumably membrane based, interaction, requires further study...
  51. ncbi request reprint Identification of Nore1 as a potential Ras effector
    D Vavvas
    The Diabetes Unit and Medical Services and the Department of Medicine, Harvard Medical School, Massachusetts General Hospital East, Charlestown, Massachusetts 02129, USA
    J Biol Chem 273:5439-42. 1998
    ..Nore1 becomes associated with Ras in situ following activation of epidermal growth factor receptor in COS-7 and in KB cells...
  52. ncbi request reprint Calyculin A-induced vimentin phosphorylation sequesters 14-3-3 and displaces other 14-3-3 partners in vivo
    G Tzivion
    Diabetes Unit, The Department of Molecular Biology, Massachusetts General Hospital, Boston, Massachusetts 02114, USA
    J Biol Chem 275:29772-8. 2000
    ..Thus, phosphovimentin, by sequestering 14-3-3 and limiting its availability to other target proteins can affect intracellular signaling processes that require 14-3-3...
  53. ncbi request reprint Raf-1 activates MAP kinase-kinase
    J M Kyriakis
    Diabetes Unit, Medical Services, Massachusetts General Hospital, Charlestown 02129
    Nature 358:417-21. 1992
    ..These results indicate that c-Raf-1 is an immediate upstream activator of MAPK-K in vivo. To our knowledge, MAPK-K is the first physiological substrate of the c-raf-1 protooncogene product to be identified...
  54. ncbi request reprint Activation of the SAPK pathway by the human STE20 homologue germinal centre kinase
    C M Pombo
    Diabetes Research Laboratory, Massachusetts General Hospital East, Charlestown, USA
    Nature 377:750-4. 1995
    ..Activation of the SAPK pathway by GCK illustrates further the striking conservation of eukaryotic signalling mechanisms and defines the first physiological function of a mammalian Ste20...
  55. ncbi request reprint Normal and oncogenic p21ras proteins bind to the amino-terminal regulatory domain of c-Raf-1
    X F Zhang
    Diabetes Unit, Harvard Medical School, Charlestown, Massachusetts
    Nature 364:308-13. 1993
    ..Raf-1 (1-257) binds GTP-Ras in preference to GDP-Ras, and inhibits Ras-GAP activity. Mutations in and around the Ras effector domain impair Ras binding to Raf-1 (1-257) and Ras transforming activity in parallel...
  56. ncbi request reprint Identification of the 14.3.3 zeta domains important for self-association and Raf binding
    Z J Luo
    Diabetes Research Laboratory, Massachusetts General Hospital, Charlestown 02129, USA
    J Biol Chem 270:23681-7. 1995
    ..In addition, Raf polypeptides bound to truncated 14.3.3 polypeptides are unable to undergo activation in situ, indicating that 14.3.3 participates in the process of Raf activation by mechanisms that remain to be elucidated...
  57. ncbi request reprint Actin-binding protein-280 binds the stress-activated protein kinase (SAPK) activator SEK-1 and is required for tumor necrosis factor-alpha activation of SAPK in melanoma cells
    A Marti
    Diabetes Unit and Medical Services, Massachusetts General Hospital and Harvard Medical School, Boston, Massachusetts 021291, USA
    J Biol Chem 272:2620-8. 1997
    ..ABP-280 participates in TNF-alpha signal transduction to SAPKs, in part through the binding of SEK-1...
  58. ncbi request reprint Regulation of an epitope-tagged recombinant Rsk-1 S6 kinase by phorbol ester and erk/MAP kinase
    J R Grove
    Diabetes Unit, Massachusetts General Hospital, Boston
    Biochemistry 32:7727-38. 1993
    ..abstract truncated at 400 words)..
  59. ncbi request reprint Raptor, a binding partner of target of rapamycin (TOR), mediates TOR action
    Kenta Hara
    Biosignal Research Center, Kobe University, 657 8501, Kobe, Japan
    Cell 110:177-89. 2002
    ..elegans raptor yields an array of phenotypes that closely resemble those produced by inactivation of Ce-TOR. Thus, raptor is an essential scaffold for the mTOR-catalyzed phosphorylation of 4EBP1 and mediates TOR action in vivo...
  60. pmc The proline-rich Akt substrate of 40 kDa (PRAS40) is a physiological substrate of mammalian target of rapamycin complex 1
    Noriko Oshiro
    Biosignal Research Center, Kobe University, Kobe 657 8501, Japan
    J Biol Chem 282:20329-39. 2007
    ..Moreover, they indicate that the ability of raptor to bind endogenous substrates is limiting for the activity of mTORC1 in vivo and is therefore a potential locus of regulation...
  61. pmc A Rictor-Myo1c complex participates in dynamic cortical actin events in 3T3-L1 adipocytes
    G Nana Hagan
    Program in Molecular Medicine, University of Massachusetts Medical School, 373 Plantation Street, Worcester, MA 01605, USA
    Mol Cell Biol 28:4215-26. 2008
    ..Taken together, our findings suggest that the Rictor-Myo1c complex is distinct from mTORC2 and that Myo1c, in conjunction with Rictor, participates in cortical actin remodeling events...
  62. ncbi request reprint The mammalian target of rapamycin (mTOR) partner, raptor, binds the mTOR substrates p70 S6 kinase and 4E-BP1 through their TOR signaling (TOS) motif
    Hiroki Nojima
    Biosignal Research Center, Kobe University, 1 1 Rokkodai cho, Nada Ku, Kobe 657 8501, Japan
    J Biol Chem 278:15461-4. 2003
    ....
  63. ncbi request reprint 14-3-3 proteins: active cofactors in cellular regulation by serine/threonine phosphorylation
    Guri Tzivion
    Cardiovascular Research Institute, Division of Molecular Cardiology, Texas A and M University System Health Science Center, College of Medicine, Temple, Texas 76504, USA
    J Biol Chem 277:3061-4. 2002
  64. ncbi request reprint RASSF3 and NORE1: identification and cloning of two human homologues of the putative tumor suppressor gene RASSF1
    Stella Tommasi
    Biology Department, Beckman Research Institute of the City of Hope, Duarte, California, CA 91010, USA
    Oncogene 21:2713-20. 2002
    ..However, aberrations in tumors have so far not been found. The presence of a Ras association domain common to NORE1, RASSF1, and RASSF3 suggests their possible involvement in Ras-like signaling pathways...
  65. ncbi request reprint Dissociation of raptor from mTOR is a mechanism of rapamycin-induced inhibition of mTOR function
    Noriko Oshiro
    Biosignal Research Center, Kobe University, Kobe 657 8501, Japan
    Genes Cells 9:359-66. 2004
    ....
  66. pmc Significance of 14-3-3 self-dimerization for phosphorylation-dependent target binding
    Ying H Shen
    Cardiovascular Research Institute, Division of Molecular Cardiology, The Texas A and M University System Health Science Center, College of Medicine, Temple, Texas 76504, USA
    Mol Biol Cell 14:4721-33. 2003
    ..These findings establish a significant role of 14-3-3 dimerization in its ability to bind targets in a phosphorylation-dependent manner and point to a mechanism in which 14-3-3 phosphorylation and dimerization counterregulate each other...

Research Grants29

  1. MOLECULAR BASIS OF CELL GROWTH CONTROL BY THE TOR KINASE
    Joseph Avruch; Fiscal Year: 2006
    ..Finally, we will characterize in vitro the basis for the radically different TOR kinase activity toward p70 S6K and 4E BP, and seek to identify the molecular basis for mTOR regulation in vivo. ..
  2. PHOSPHOPEPTIDE METABOLISM IN ADIPOCYTES
    Joseph Avruch; Fiscal Year: 2007
    ..These results will have implications for the design of new pharmacologic interventions in diabetes mellitus and will have wide implications for the nutritional regulation of body protein turnover. ..
  3. MOLECULAR BASIS OF CELL GROWTH CONTROL BY THE TOR KINASE
    Joseph Avruch; Fiscal Year: 2007
    ..The results of these studies will provide a basis for therapeutic interventions in this pathway, which is crucial to both human cancers and to diseases like Type 2 diabetes ..
  4. TRAINING PROGRAM IN ENDOCRINOLOGY AND DIABETES
    Joseph Avruch; Fiscal Year: 2007
    ..The institutional training grant represents the central stabilizing financial element in this program, and is especially critical in enabling M.D. trainees to achieve careers in biomedical investigation ..
  5. MOLECULAR BASIS OF CELL GROWTH CONTROL BY THE TOR KINASE
    Joseph Avruch; Fiscal Year: 2009
    ..The results of these studies will provide basis for therapeutic interventions in this pathway, which is crucial to both human cancers and to diseases like Type 2 diabetes ..
  6. Decoding the MST1 and MST2 kinases in cellular physiology and tumor suppression
    Nabeel Bardeesy; Fiscal Year: 2010
    ..We want to find out how they are regulated, the identity of their key targets in suppressing tumor development, how their removal enables liver cancer to develop and their role in human liver cancer. ..
  7. MOLECULAR BASIS OF CELL GROWTH CONTROL BY THE TOR KINASE
    Joseph Avruch; Fiscal Year: 2001
    ..These studies will define a new signal transduction pathway controlling cell growth in lymphoid and other cells. ..
  8. MOLECULAR BASIS OF CELL GROWTH CONTROL BY THE TOR KINASE
    Joseph Avruch; Fiscal Year: 2011
    ..The results of these studies will provide basis for therapeutic interventions in this pathway, which is crucial to both human cancers and to diseases like Type 2 diabetes ..