L C Cantley

Summary

Affiliation: Harvard University
Country: USA

Publications

  1. ncbi The phosphoinositide 3-kinase pathway
    Lewis C Cantley
    Department of Cell Biology, Harvard Medical School and Division of Signal Transduction, Beth Israel Deaconess Medical Center, Boston, MA 02115 5713, USA
    Science 296:1655-7. 2002
  2. ncbi New insights into tumor suppression: PTEN suppresses tumor formation by restraining the phosphoinositide 3-kinase/AKT pathway
    L C Cantley
    Department of Cell Biology, Harvard Medical School, Boston, MA 02115, USA
    Proc Natl Acad Sci U S A 96:4240-5. 1999
  3. ncbi Differential signaling by the epidermal growth factor-like growth factors neuregulin-1 and neuregulin-2
    C S Crovello
    Division of Signal Transduction, Beth Israel Deaconess Medical Center and the Department of Cell Biology, Harvard Medical School, Boston, Massachusetts 02215, USA
    J Biol Chem 273:26954-61. 1998
  4. ncbi Association of protein kinase Cmu with type II phosphatidylinositol 4-kinase and type I phosphatidylinositol-4-phosphate 5-kinase
    K Nishikawa
    Division of Signal Transduction, Beth Israel Deaconess Medical Center and Department of Cell Biology, Harvard Medical School, Boston, Massachusetts 02115, USA
    J Biol Chem 273:23126-33. 1998
  5. ncbi Crystal structures of the XLP protein SAP reveal a class of SH2 domains with extended, phosphotyrosine-independent sequence recognition
    F Poy
    Department of Cancer Biology, Dana Farber Cancer Institute, Boston, Massachusetts 02115, USA
    Mol Cell 4:555-61. 1999
  6. ncbi Extracellular HIV-1 Tat protein induces a rapid and selective activation of protein kinase C (PKC)-alpha, and -epsilon and -zeta isoforms in PC12 cells
    P Borgatti
    Division of Signal Transduction, Harvard Institute of Medicine, Beth Israel Hospital, Boston, Massachusettes 02115, USA
    Biochem Biophys Res Commun 242:332-7. 1998
  7. ncbi p120cbl is a cytosolic adapter protein that associates with phosphoinositide 3-kinase in response to epidermal growth factor in PC12 and other cells
    S P Soltoff
    Department of Medicine, Beth Israel Hospital, Boston, Massachusetts 02115, USA
    J Biol Chem 271:563-7. 1996
  8. ncbi TAZ: a novel transcriptional co-activator regulated by interactions with 14-3-3 and PDZ domain proteins
    F Kanai
    Division of Signal Transduction, Department of Medicine and Department of Surgery, Beth Israel Deaconess Medical Center, Department of Cell Biology, Harvard Medical School, Boston, MA 02115, USA
    EMBO J 19:6778-91. 2000
  9. ncbi Ligand discrimination in signaling through an ErbB4 receptor homodimer
    C Sweeney
    Department of Cell Biology, Harvard Medical School and Division of Signal Transduction, Beth Israel Deaconess Medical Center, Boston, Massachusetts 02215, USA
    J Biol Chem 275:19803-7. 2000
  10. ncbi Type Ialpha phosphatidylinositol-4-phosphate 5-kinase mediates Rac-dependent actin assembly
    K F Tolias
    Division of Signal Transduction, Departments of Cell Biology, Beth Israel Deaconess Medical Center, Harvard Medical School, Boston 02115, USA
    Curr Biol 10:153-6. 2000

Detail Information

Publications128 found, 100 shown here

  1. ncbi The phosphoinositide 3-kinase pathway
    Lewis C Cantley
    Department of Cell Biology, Harvard Medical School and Division of Signal Transduction, Beth Israel Deaconess Medical Center, Boston, MA 02115 5713, USA
    Science 296:1655-7. 2002
    ..The PI3K pathway is implicated in human diseases including diabetes and cancer, and understanding the intricacies of this pathway may provide new avenues for therapuetic intervention...
  2. ncbi New insights into tumor suppression: PTEN suppresses tumor formation by restraining the phosphoinositide 3-kinase/AKT pathway
    L C Cantley
    Department of Cell Biology, Harvard Medical School, Boston, MA 02115, USA
    Proc Natl Acad Sci U S A 96:4240-5. 1999
    ..PTEN appears to negatively control the phosphoinositide 3-kinase signaling pathway for regulation of cell growth and survival by dephosphorylating the 3 position of phosphoinositides...
  3. ncbi Differential signaling by the epidermal growth factor-like growth factors neuregulin-1 and neuregulin-2
    C S Crovello
    Division of Signal Transduction, Beth Israel Deaconess Medical Center and the Department of Cell Biology, Harvard Medical School, Boston, Massachusetts 02215, USA
    J Biol Chem 273:26954-61. 1998
    ..Since both of these cell lines express only two of the known ErbB receptors, our results imply that EGF-like ligands might elicit differential signaling within the context of a single receptor heterodimer...
  4. ncbi Association of protein kinase Cmu with type II phosphatidylinositol 4-kinase and type I phosphatidylinositol-4-phosphate 5-kinase
    K Nishikawa
    Division of Signal Transduction, Beth Israel Deaconess Medical Center and Department of Cell Biology, Harvard Medical School, Boston, Massachusetts 02115, USA
    J Biol Chem 273:23126-33. 1998
    ..These results suggest a novel model in which the non-catalytic region of PKCmu acts as a scaffold for assembly of enzymes involved in phosphoinositide synthesis at specific membrane locations...
  5. ncbi Crystal structures of the XLP protein SAP reveal a class of SH2 domains with extended, phosphotyrosine-independent sequence recognition
    F Poy
    Department of Cancer Biology, Dana Farber Cancer Institute, Boston, Massachusetts 02115, USA
    Mol Cell 4:555-61. 1999
    ..Further, we show that SAP and the similar protein EAT-2 recognize the sequence motif TIpYXX(V/I)...
  6. ncbi Extracellular HIV-1 Tat protein induces a rapid and selective activation of protein kinase C (PKC)-alpha, and -epsilon and -zeta isoforms in PC12 cells
    P Borgatti
    Division of Signal Transduction, Harvard Institute of Medicine, Beth Israel Hospital, Boston, Massachusettes 02115, USA
    Biochem Biophys Res Commun 242:332-7. 1998
    ..Taken together, these findings demonstrate that extracellular Tat shows a cytokine-like activity in PC12 cells, being able to trigger an intracellular signalling cascade which involves PKC-alpha, -epsilon, and -zeta...
  7. ncbi p120cbl is a cytosolic adapter protein that associates with phosphoinositide 3-kinase in response to epidermal growth factor in PC12 and other cells
    S P Soltoff
    Department of Medicine, Beth Israel Hospital, Boston, Massachusetts 02115, USA
    J Biol Chem 271:563-7. 1996
    ..p120cbl was also present in A431 cells and offers an additional pathway by which EGF can activate PI 3-kinase in these cells...
  8. ncbi TAZ: a novel transcriptional co-activator regulated by interactions with 14-3-3 and PDZ domain proteins
    F Kanai
    Division of Signal Transduction, Department of Medicine and Department of Surgery, Beth Israel Deaconess Medical Center, Department of Cell Biology, Harvard Medical School, Boston, MA 02115, USA
    EMBO J 19:6778-91. 2000
    ..TAZ may link events at the plasma membrane and cytoskeleton to nuclear transcription in a manner that can be regulated by 14-3-3...
  9. ncbi Ligand discrimination in signaling through an ErbB4 receptor homodimer
    C Sweeney
    Department of Cell Biology, Harvard Medical School and Division of Signal Transduction, Beth Israel Deaconess Medical Center, Boston, Massachusetts 02215, USA
    J Biol Chem 275:19803-7. 2000
    ..More generally, our observations significantly modify our understanding of signaling through receptor tyrosine kinases and point to a number of possible models for ligand-mediated signal diversification...
  10. ncbi Type Ialpha phosphatidylinositol-4-phosphate 5-kinase mediates Rac-dependent actin assembly
    K F Tolias
    Division of Signal Transduction, Departments of Cell Biology, Beth Israel Deaconess Medical Center, Harvard Medical School, Boston 02115, USA
    Curr Biol 10:153-6. 2000
    ..These results demonstrate that PIP 5-kinase alpha is a critical mediator of thrombin- and Rac-dependent actin assembly...
  11. ncbi Src-homology 3 domain of protein kinase p59fyn mediates binding to phosphatidylinositol 3-kinase in T cells
    K V Prasad
    Division of Tumor Immunology, Dana Farber Cancer Institute, Boston, MA 02115
    Proc Natl Acad Sci U S A 90:7366-70. 1993
    ..Thus PI 3-kinase is a target of SH3 domains and is likely to play a major role in the signals derived from the TCR zeta/CD3-p59fyn complex...
  12. ncbi Impaired kit- but not FcepsilonRI-initiated mast cell activation in the absence of phosphoinositide 3-kinase p85alpha gene products
    J M Lu-Kuo
    Department of Medicine, Harvard Medical School, Boston, Massachusetts 02115, USA
    J Biol Chem 275:6022-9. 2000
    ....
  13. ncbi Characterization of a Rac1- and RhoGDI-associated lipid kinase signaling complex
    K F Tolias
    Beth Israel Deaconess Medical Center, and Department of Cell Biology, Harvard Medical School, Boston, Massachusetts, USA
    Mol Cell Biol 18:762-70. 1998
    ....
  14. ncbi Phosphatidylinositol 3-kinase-dependent activation of trypsinogen modulates the severity of acute pancreatitis
    V P Singh
    Department of Surgery, Beth Israel Deaconess Medical Center and Harvard Medical School, Boston, Massachusetts 02215, USA
    J Clin Invest 108:1387-95. 2001
    ..Our observations suggest that phosphatidylinositol 3-kinase inhibition might be of benefit in preventing acute pancreatitis...
  15. ncbi Conditional inhibition of the mitogen-activated protein kinase cascade by wortmannin. Dependence on signal strength
    B C Duckworth
    Department of Medicine, Division of Signal Transduction, Beth Israel Hospital, Boston, Massachusetts 02115, USA
    J Biol Chem 272:27665-70. 1997
    ..We present evidence that a protein kinase C family member downstream of phospholipase Cgamma is involved in the redundant pathway...
  16. ncbi Cloning and characterization of a wortmannin-sensitive human phosphatidylinositol 4-kinase
    R Meyers
    Department of Cell Biology, Harvard Medical School and Division of Signal Transduction, Beth Israel Hospital, Boston, Massachusetts 02215, USA
    J Biol Chem 272:4384-90. 1997
    ..Catt, J. K., and Balla, T. (1995) Proc. Natl. Acad. Sci. U. S. A. 92, 5317-5321)...
  17. ncbi Identification of the tuberous sclerosis complex-2 tumor suppressor gene product tuberin as a target of the phosphoinositide 3-kinase/akt pathway
    Brendan D Manning
    Department of Cell Biology, Harvard Medical School, Boston, Massachusetts 02115, USA
    Mol Cell 10:151-62. 2002
    ..Finally, we find that a tuberin mutant lacking the major PI3K-dependent phosphorylation sites can block the activation of S6K1, suggesting a means by which the PI3K-Akt pathway regulates S6K1 activity...
  18. ncbi The structural basis for 14-3-3:phosphopeptide binding specificity
    M B Yaffe
    Department of Medicine, Beth Israel Deaconess Medical Center, Boston, Massachusetts 02215, USA
    Cell 91:961-71. 1997
    ..Finally, we show that the 14-3-3 dimer binds tightly to single molecules containing tandem repeats of phosphoserine motifs, implicating bidentate association as a signaling mechanism with molecules such as Raf, BAD, and Cbl...
  19. ncbi Determination of protease cleavage site motifs using mixture-based oriented peptide libraries
    B E Turk
    Department of Medicine, Beth Israel Deaconess Medical Center, Department of Cell Biology, Harvard Medical School, 330 Brookline Avenue, Boston, MA 02215, USA
    Nat Biotechnol 19:661-7. 2001
    ..Our results indicate that a small set of libraries can be used to quickly profile an expanding protease family, providing information applicable to the design of inhibitors and to the identification of protein substrates...
  20. ncbi Determination of the specific substrate sequence motifs of protein kinase C isozymes
    K Nishikawa
    Division of Signal Transduction, Beth Israel Hospital, Boston, Massachusetts 02115, USA
    J Biol Chem 272:952-60. 1997
    ..The structural basis for the selectivity of PKC isozymes is discussed based on residues predicted to form the catalytic cleft...
  21. ncbi Type I phosphatidylinositol-4-phosphate 5-kinases synthesize the novel lipids phosphatidylinositol 3,5-bisphosphate and phosphatidylinositol 5-phosphate
    K F Tolias
    Division of Signal Transduction, Beth Israel Deaconess Medical Center, Boston, Massachusetts 02115, USA
    J Biol Chem 273:18040-6. 1998
    ..The ability of PIP5Ks to produce multiple signaling molecules indicates that they may participate in a variety of cellular processes...
  22. ncbi Activation of P2Y2 receptors by UTP and ATP stimulates mitogen-activated kinase activity through a pathway that involves related adhesion focal tyrosine kinase and protein kinase C
    S P Soltoff
    Division of Signal Transduction, Beth Israel Deaconess Medical Center, Boston, Massachusetts 02215, USA
    J Biol Chem 273:2653-60. 1998
    ..These results suggest that the P2Y2 receptor-initiated activation of MAP kinase was dependent on the elevation of [Ca2+]i, involved the recruitment of Shc and Grb2, and was mediated by RAFTK and PKC...
  23. ncbi United at last: the tuberous sclerosis complex gene products connect the phosphoinositide 3-kinase/Akt pathway to mammalian target of rapamycin (mTOR) signalling
    B D Manning
    Department of Cell Biology, Harvard Medical School, Division of Signal Transduction, Beth Israel Deaconess Medical Center, 4 Blackfan Circle, Boston, MA 02115, USA
    Biochem Soc Trans 31:573-8. 2003
    ....
  24. ncbi The Cbl phosphotyrosine-binding domain selects a D(N/D)XpY motif and binds to the Tyr292 negative regulatory phosphorylation site of ZAP-70
    M L Lupher
    Lymphocyte Biology Section, Division of Rheumatology, Immunology and Allergy, Department of Medicine, Brigham and Women s Hospital, Boston, Massachusetts 02115, USA
    J Biol Chem 272:33140-4. 1997
    ..These results identify a potential Cbl-PTB domain-dependent role for Cbl in the negative regulation of ZAP-70 and predict potential Cbl-PTB domain binding sites on other protein tyrosine kinases known to interact with Cbl...
  25. ncbi Impaired B cell development and proliferation in absence of phosphoinositide 3-kinase p85alpha
    D A Fruman
    Division of Signal Transduction, Beth Israel Deaconess Medical Center, Boston, MA 02215, USA
    Science 283:393-7. 1999
    ..In contrast, T cell development and proliferation was normal. This phenotype is similar to defects observed in mice lacking the tyrosine kinase Btk...
  26. ncbi The tumor suppressor LKB1 kinase directly activates AMP-activated kinase and regulates apoptosis in response to energy stress
    Reuben J Shaw
    Department of Systems Biology, Harvard Medical School, and Division of Signal Transduction, Beth Israel Deaconess Medical Center, Boston, MA 02215, USA
    Proc Natl Acad Sci U S A 101:3329-35. 2004
    ..The role of LKB1/AMPK in the survival of a subset of genetically defined tumor cells may provide opportunities for cancer therapeutics...
  27. ncbi The SRC-associated protein CUB Domain-Containing Protein-1 regulates adhesion and motility
    C H Benes
    Department of Medicine, Division of Signal Transduction, Beth Israel Deaconess Medical Center, Boston, MA 02215, USA
    Oncogene 31:653-63. 2012
    ..Thus, signaling events that accompany the CDCP1 tyrosine phosphorylation observed in cell lines and human lung tumors may explain how the CDCP1/SFK complex regulates motility and adhesion...
  28. ncbi The erbB3 gene product is a receptor for heregulin
    K L Carraway
    Department of Cell Biology, Harvard Medical School, Boston, Massachusetts
    J Biol Chem 269:14303-6. 1994
    ..We conclude that ErbB3 is a receptor for HRG and is capable of mediating HRG-stimulated tyrosine phosphorylation of itself and p185erbB2/neu in cells that express both receptors...
  29. ncbi Phosphoinositide kinases
    D A Fruman
    Department of Medicine, Beth Israel Deaconess Medical Center, Boston, Massachusetts 02215, USA
    Annu Rev Biochem 67:481-507. 1998
    ..Recent advances have challenged previous hypotheses about the substrate selectivity of different phosphoinositide kinase families. Here we re-examine the pathways of phosphoinositide synthesis and the enzymes involved...
  30. ncbi Subcellular locations of phosphatidylinositol 4-kinase isoforms
    K Wong
    Department of Cell Biology, Harvard Medical School, Boston, Massachusetts 02115, USA
    J Biol Chem 272:13236-41. 1997
    ..Neither of these isoforms accounts for the major type II PtdIns 4-kinase activity detected in the lysosomes and plasma membrane fraction...
  31. ncbi Vascular dysmorphogenesis caused by an activating mutation in the receptor tyrosine kinase TIE2
    M Vikkula
    Department of Cell Biology, Harvard Medical School, Boston, Massachusetts 02115, USA
    Cell 87:1181-90. 1996
    ..We conclude that an activating mutation in TIE2 causes inherited VMs in the two families and that the TIE2 signaling pathway is critical for endothelial cell-smooth muscle cell communication in venous morphogenesis...
  32. ncbi A new pathway for synthesis of phosphatidylinositol-4,5-bisphosphate
    L E Rameh
    Department of Cell Biology, Harvard Medical School, Boston, Massachusetts 02115, USA
    Nature 390:192-6. 1997
    ..Although PtdIns-5-P was previously thought not to exist in vivo, we find evidence for the presence of this lipid in mammalian fibroblasts, establishing a new pathway for PtdIns-4,5-P2 synthesis...
  33. ncbi Biochemistry. PI3K charges ahead
    Jennifer Y Lee
    Department of Systems Biology, Harvard Medical School and Division of Signal Transduction, Beth Israel Deaconess Medical Center, Boston, MA 02115, USA
    Science 317:206-7. 2007
  34. ncbi The LKB1 tumor suppressor negatively regulates mTOR signaling
    Reuben J Shaw
    Department of Systems Biology, Harvard Medical School and Division of Signal Transduction, Beth Israel Deaconess Medical Center, Boston, Massachusetts 02115, USA
    Cancer Cell 6:91-9. 2004
    ..These findings position aberrant mTOR activation at the nexus of these germline neoplastic conditions and suggest the use of mTOR inhibitors in the treatment of Peutz-Jeghers syndrome...
  35. ncbi DNA damage-induced association of ATM with its target proteins requires a protein interaction domain in the N terminus of ATM
    Norvin Fernandes
    Department of Radiation Oncology, Harvard Medical School, Dana Farber Cancer Institute, Boston, Massachusetts 02115, USA
    J Biol Chem 280:15158-64. 2005
    ..Furthermore, this domain of ATM is required for ATM to form nuclear foci following exposure to ionizing radiation...
  36. ncbi Tuberous sclerosis complex gene products, Tuberin and Hamartin, control mTOR signaling by acting as a GTPase-activating protein complex toward Rheb
    Andrew R Tee
    Department of Cell Biology, Harvard Medical School, Boston, MA 02115, USA
    Curr Biol 13:1259-68. 2003
    ..Tuberin and Hamartin form a tumor suppressor heterodimer that inhibits the mammalian target of rapamycin (mTOR) nutrient signaling input, but how this occurs is unclear...
  37. ncbi Evidence for an alternative glycolytic pathway in rapidly proliferating cells
    Matthew G Vander Heiden
    Dana Farber Cancer Institute, Harvard Medical School, Boston, MA 02115, USA
    Science 329:1492-9. 2010
    ....
  38. ncbi Structural organization and alternative splicing of the murine phosphoinositide 3-kinase p85 alpha gene
    D A Fruman
    Division of Signal Transduction, Beth Israel Hospital, Boston, Massachusetts, USA
    Genomics 37:113-21. 1996
    ..Northern blot analysis of mouse tissues reveals differential expression of full-length and alternatively spliced p85 alpha, with the splice variant most abundant in the liver...
  39. ncbi The conserved phosphoinositide 3-kinase pathway determines heart size in mice
    T Shioi
    Cardiovascular Division, Beth Israel Deaconess Medical Center and Departments of Medicine and Cell Biology, Harvard Medical School, Boston, MA 02215, USA
    EMBO J 19:2537-48. 2000
    ..Thus, the PI3K pathway is necessary and sufficient to promote organ growth in mammals...
  40. ncbi MET amplification leads to gefitinib resistance in lung cancer by activating ERBB3 signaling
    Jeffrey A Engelman
    Massachusetts General Hospital Cancer Center, Boston, MA 02114, USA
    Science 316:1039-43. 2007
    ..Thus, we propose that MET amplification may promote drug resistance in other ERBB-driven cancers as well...
  41. ncbi Tuberous sclerosis complex-1 and -2 gene products function together to inhibit mammalian target of rapamycin (mTOR)-mediated downstream signaling
    Andrew R Tee
    Department of Cell Biology, Harvard Medical School, Boston, MA 02115, USA
    Proc Natl Acad Sci U S A 99:13571-6. 2002
    ....
  42. ncbi Crystal structure of the breakpoint cluster region-homology domain from phosphoinositide 3-kinase p85 alpha subunit
    A Musacchio
    Laboratory of Molecular Medicine, Children s Hospital, Boston, MA 02115, USA
    Proc Natl Acad Sci U S A 93:14373-8. 1996
    ..Their packing suggests the location of a G-protein binding site. This structure of a GAP-like domain for small GTP-binding proteins provides a framework for analyzing the function of this class of molecules...
  43. ncbi PI3K pathway alterations in cancer: variations on a theme
    T L Yuan
    Department of Systems Biology, Harvard Medical School and Division of Signal Transduction, Beth Israel Deaconess Medical Center, Boston, MA 2115, USA
    Oncogene 27:5497-510. 2008
    ..In this review, we will examine the oncogenic properties of these genetic alterations to understand whether they are redundant or distinct and propose treatment strategies tailored for these genetic lesions...
  44. ncbi Rho family GTPases bind to phosphoinositide kinases
    K F Tolias
    Department of Cell Biology, Harvard Medical School, Boston, Massachusetts, USA
    J Biol Chem 270:17656-9. 1995
    ....
  45. ncbi Mouse phosphoinositide 3-kinase p110alpha gene: cloning, structural organization, and localization to chromosome 3 band B
    I A Aksoy
    Dana Farber Cancer Institute, Harvard Medical School, Boston, Massachusetts, 02115, USA
    Biochem Biophys Res Commun 262:438-42. 1999
    ..FISH results and DAPI banding demonstrated localization of the p110alpha gene to band B on mouse chromosome 3, a region syntenic with human chromosome 3q26.3...
  46. ncbi Growth factor-specific signaling pathway stimulation and gene expression mediated by ErbB receptors
    C Sweeney
    Department of Cell Biology, Harvard Medical School and Division of Signal Transduction, Beth Israel Deaconess Medical Center, Boston, Massachusetts 02215, USA
    J Biol Chem 276:22685-98. 2001
    ..Our observations also suggest that the identity and kinetics of signaling pathway usage by RTKs may play a role in the selection of regulated genes...
  47. ncbi Direct regulation of the Akt proto-oncogene product by phosphatidylinositol-3,4-bisphosphate
    T F Franke
    ABL Basic Research Program, National Cancer Institute Frederick Cancer Research Facility and Development Center NCI FCRFDC, Frederick, MD 21702, USA
    Science 275:665-8. 1997
    ..Thus, Akt is apparently regulated by the direct interaction of PtdIns-3,4-P2 with the Akt PH domain...
  48. ncbi Signalling through the lipid products of phosphoinositide-3-OH kinase
    A Toker
    Boston Biomedical Research Institute, Massachusetts 02114, USA
    Nature 387:673-6. 1997
    ..But how PI(3)K mediates these responses is only now becoming clear...
  49. ncbi ErbB-3 mediates phosphoinositide 3-kinase activity in gefitinib-sensitive non-small cell lung cancer cell lines
    Jeffrey A Engelman
    Department of Systems Biology, Harvard Medical School, 77 Avenue Louis Pasteur, Boston, MA 02115, USA
    Proc Natl Acad Sci U S A 102:3788-93. 2005
    ..We conclude that ErbB-3 is used to couple EGFR to the PI3K/Akt pathway in gefitinib-sensitive NSCLC cell lines harboring WT and mutant EGFRs...
  50. ncbi Identification and characterization of a phosphoinositide phosphate kinase homolog
    James D Chang
    Beth Israel Deaconess Medical Center, Divisions of Signal Transduction, Cardiovascular Medicine, and Hematology Oncology, Boston, Massachusetts 02215, USA
    J Biol Chem 279:11672-9. 2004
    ..These results suggest that PIPKH acts as a scaffold to localize and regulate type I PI(4)P 5-kinases and the synthesis of PI(3,4,5)P(3)...
  51. ncbi The kinase LKB1 mediates glucose homeostasis in liver and therapeutic effects of metformin
    Reuben J Shaw
    Department of Systems Biology, Harvard Medical School, Boston, MA 02115, USA
    Science 310:1642-6. 2005
    ..Finally, we show that metformin, one of the most widely prescribed type 2 diabetes therapeutics, requires LKB1 in the liver to lower blood glucose levels...
  52. ncbi Differential regulation of the phosphoinositide 3-kinase and MAP kinase pathways by hepatocyte growth factor vs. insulin-like growth factor-I in myogenic cells
    Orna Halevy
    Division of Signal Transduction, Beth Israel Deaconess Medical Center, Department of Cell Biology, Harvard Medical School, Boston, MA 02115, USA
    Exp Cell Res 297:224-34. 2004
    ..Moreover, the finding that PI3K activity is required for HGF-induced MAPK activation suggests its additional role in proliferation, rather than exclusively in the differentiation of adult myoblasts...
  53. ncbi Feedback inhibition of Akt signaling limits the growth of tumors lacking Tsc2
    Brendan D Manning
    Department of Genetics and Complex Diseases, Harvard School of Public Health, Boston, Massachusetts 02115, USA
    Genes Dev 19:1773-8. 2005
    ..However, Pten haploinsufficiency restores Akt signaling in these tumors and dramatically enhances their severity. This study demonstrates that attenuation of the PI3K-Akt pathway in tumors lacking TSC2 contributes to their benign nature...
  54. ncbi Protein sequences from mastodon and Tyrannosaurus rex revealed by mass spectrometry
    John M Asara
    Division of Signal Transduction, Beth Israel Deaconess Medical Center, Boston, MA 02115, USA
    Science 316:280-5. 2007
    ....
  55. ncbi In-gel stable isotope labeling for relative quantification using mass spectrometry
    John M Asara
    Division of Signal Transduction, Beth Israel Deaconess Medical Center, Boston, Massachusetts 02115, USA
    Nat Protoc 1:46-51. 2006
    ..This protocol should take approximately 24-26 h to complete, including the incubation time for proteolytic digestion. Additional time will be needed for data analysis and interpretation...
  56. ncbi In-Gel Stable-Isotope Labeling (ISIL): a strategy for mass spectrometry-based relative quantification
    John M Asara
    Division of Signal Transduction, Beth Israel Deaconess Medical Center, Boston, Massachusetts 02115, USA
    J Proteome Res 5:155-63. 2006
    ..An advantage of ISIL is that visualization of gel differences can be used as a first quantification step followed by accurate and sensitive protein level stable-isotope labeling and mass spectrometry-based relative quantification...
  57. ncbi Divergent regulation of hepatic glucose and lipid metabolism by phosphoinositide 3-kinase via Akt and PKClambda/zeta
    Cullen M Taniguchi
    Cellular and Molecular Physiology, Joslin Diabetes Center, Harvard Medical School, Boston, MA 02215, USA
    Cell Metab 3:343-53. 2006
    ....
  58. ncbi Loss of class IA PI3K signaling in muscle leads to impaired muscle growth, insulin response, and hyperlipidemia
    Ji Luo
    Department of Systems Biology, Harvard Medical School, Beth Israel Deaconess Medical Center, Boston, MA 02115, USA
    Cell Metab 3:355-66. 2006
    ..Our finding also indicates that compromised muscle PI3K signaling could contribute to symptoms of hyperlipidemia associated with human type 2 diabetes...
  59. ncbi Rheb fills a GAP between TSC and TOR
    Brendan D Manning
    Department of Cell Biology, Harvard Medical School, Division of Signal Transduction, Beth Israel Deaconess Medical Center, Harvard Institutes of Medicine, Rm 1028, 4 Blackfan Circle, Boston, MA 02115, USA
    Trends Biochem Sci 28:573-6. 2003
    ....
  60. ncbi AKT/PKB signaling: navigating downstream
    Brendan D Manning
    Department of Genetics and Complex Diseases, Harvard School of Public Health, SPH2 117, Boston, MA 02115, USA
    Cell 129:1261-74. 2007
    ..In addition, we discuss those Akt substrates that are most likely to contribute to the diverse cellular roles of Akt, which include cell survival, growth, proliferation, angiogenesis, metabolism, and migration...
  61. ncbi Phosphorylation of the tumor suppressor CYLD by the breast cancer oncogene IKKepsilon promotes cell transformation
    Jessica E Hutti
    Department of Systems Biology, Harvard Medical School, Boston, MA 02115, USA
    Mol Cell 34:461-72. 2009
    ..Together, these observations define IKKepsilon and CYLD as an oncogene-tumor suppressor network that participates in tumorigenesis...
  62. ncbi Understanding the Warburg effect: the metabolic requirements of cell proliferation
    Matthew G Vander Heiden
    Department of Medical Oncology, Dana Farber Cancer Institute, Boston, MA 02115, USA
    Science 324:1029-33. 2009
    ..A better understanding of the mechanistic links between cellular metabolism and growth control may ultimately lead to better treatments for human cancer...
  63. ncbi The phosphoinositide 3-kinase regulatory subunit p85alpha can exert tumor suppressor properties through negative regulation of growth factor signaling
    Cullen M Taniguchi
    Joslin Diabetes Center and Department of Pathology, Harvard Medical School, Boston, Massachusetts 02215, USA
    Cancer Res 70:5305-15. 2010
    ..Together, these results substantiate the concept that the p85 subunit of PI3K has a tumor-suppressive role in the liver and possibly other tissues...
  64. ncbi Targeting the PI3K signaling pathway in cancer
    KWOK KIN WONG
    Department of Medicine, Harvard Medical School, Boston, MA 02115, United States
    Curr Opin Genet Dev 20:87-90. 2010
    ..This review focuses on their efficacy as single agents and in combination with other targeted therapies, specifically those targeting the MEK-ERK signaling pathway...
  65. ncbi PIK3CA mutation is associated with poor prognosis among patients with curatively resected colon cancer
    Shuji Ogino
    Department of Medical Oncology, Dana Farber Cancer Institute, Brigham and Women s Hospital, Harvard Medical School, 44 Binney St, Room JF 215C, Boston, MA 02115 USA
    J Clin Oncol 27:1477-84. 2009
    ..PIK3CA mutation and subsequent activation of the AKT pathway play an important role in colorectal carcinogenesis. However, little is known about the prognostic role of PIK3CA mutation in colon cancer...
  66. ncbi Altered metabolism in cancer
    Jason W Locasale
    Department of Systems Biology, Harvard Medical School, Boston, MA 02215, USA
    BMC Biol 8:88. 2010
    ..Here, we take a broader look at the regulation of energy metabolism in cancer cells, considering their anabolic as well as catabolic needs. See research article: http://www.biomedcentral.com/1752-0509/4/58/..
  67. ncbi Oncogenic B-RAF negatively regulates the tumor suppressor LKB1 to promote melanoma cell proliferation
    Bin Zheng
    Division of Signal Transduction, Beth Israel Deaconess Medical Center, Boston, MA 02115, USA
    Mol Cell 33:237-47. 2009
    ..Our findings provide a molecular linkage between the LKB1-AMPK and the RAF-MEK-ERK pathways and suggest that suppression of LKB1 function by B-RAF V600E plays an important role in B-RAF V600E-driven tumorigenesis...
  68. ncbi The M2 splice isoform of pyruvate kinase is important for cancer metabolism and tumour growth
    Heather R Christofk
    Department of Systems Biology, Harvard Medical School, Boston, Massachusetts 02115, USA
    Nature 452:230-3. 2008
    ..These results demonstrate that M2 expression is necessary for aerobic glycolysis and that this metabolic phenotype provides a selective growth advantage for tumour cells in vivo...
  69. ncbi A label-free quantification method by MS/MS TIC compared to SILAC and spectral counting in a proteomics screen
    John M Asara
    Division of Signal Transduction, Beth Israel Deaconess Medical Center, Boston, MA 02115, USA
    Proteomics 8:994-9. 2008
    ....
  70. ncbi Evidence that inositol polyphosphate 4-phosphatase type II is a tumor suppressor that inhibits PI3K signaling
    Christina Gewinner
    Division of Signal Transduction, Beth Israel Deaconess Medical Center, Department of Systems Biology, Harvard Medical School, Boston, MA 02115, USA
    Cancer Cell 16:115-25. 2009
    ....
  71. ncbi Phosphoinositide 3-kinase inhibition spares actin assembly in activating platelets but reverses platelet aggregation
    T J Kovacsovics
    Department of Medicine, Brigham and Women s Hospital, Boston, Massachusetts, USA
    J Biol Chem 270:11358-66. 1995
    ..PI 3-K stimulation downstream of GPIIb-IIIa engagement may provide positive feedback required to sustain active GPIIb-IIIa...
  72. ncbi A single point mutation switches the specificity of group III Src homology (SH) 2 domains to that of group I SH2 domains
    Z Songyang
    Division of Signal Transduction, Beth Israel Hospital, Boston, Massachusetts, USA
    J Biol Chem 270:26029-32. 1995
    ..These results establish the importance of the beta D5 residue in determining specificities of SH2 domains...
  73. ncbi Cloning and characterization of a human phosphatidylinositol 4-kinase
    K Wong
    Department of Cell Biology, Harvard Medical School, Boston, Massachusetts 02115
    J Biol Chem 269:28878-84. 1994
    ....
  74. ncbi The alternative splicing repressors hnRNP A1/A2 and PTB influence pyruvate kinase isoform expression and cell metabolism
    Cynthia V Clower
    Division of Signal Transduction, Department of Systems Biology, Beth Israel Deaconess Medical Center, Harvard Medical School, Boston, MA 02115, USA
    Proc Natl Acad Sci U S A 107:1894-9. 2010
    ..These findings extend the links between alternative splicing and cancer, and begin to define some of the factors responsible for the switch to aerobic glycolysis...
  75. ncbi Breast cancer-associated PIK3CA mutations are oncogenic in mammary epithelial cells
    Steven J Isakoff
    Department of Cell Biology, Harvard Medical School, Boston, Massachusetts 02115, USA
    Cancer Res 65:10992-1000. 2005
    ..Together, these data support the notion that the cancer-associated mutations in PIK3CA may significantly contribute to breast cancer pathogenesis and represent attractive targets for therapeutic inhibition...
  76. ncbi Allelic dilution obscures detection of a biologically significant resistance mutation in EGFR-amplified lung cancer
    Jeffrey A Engelman
    Massachusetts General Hospital Cancer Center, Boston, Massachusetts, USA
    J Clin Invest 116:2695-706. 2006
    ....
  77. ncbi PI3K enters beta-testing
    Adam J Shaywitz
    Division of Signal Transduction, Beth Israel Deaconess Medical Center, Boston, MA 02215, USA
    Cell Metab 8:179-81. 2008
    ..In a recent publication in Nature, Jia et al. (2008) identify specific functions of the p110beta isoform of PI3K in glucose metabolism, cellular proliferation, and tumorigenesis...
  78. ncbi Differential effects of gefitinib and cetuximab on non-small-cell lung cancers bearing epidermal growth factor receptor mutations
    Toru Mukohara
    Lowe Center for Thoracic Oncology, Dana-Farber Cancer Institute, Boston, MA 02115, USA
    J Natl Cancer Inst 97:1185-94. 2005
    ..003). CONCLUSIONS: EGFR mutations in NSCLC cells are associated with sensitivity to gefitinib but not to cetuximab...
  79. ncbi PtdIns(4,5)P2 functions at the cleavage furrow during cytokinesis
    Seth J Field
    Division of Signal Transduction, Beth Israel Deaconess Medical Center, Massachusetts General Hospital, Harvard Medical School, Boston, Massachusetts 02115, USA
    Curr Biol 15:1407-12. 2005
    ..We conclude that PtdIns(4,5)P2 is present at the cleavage furrow and is required for normal cytokinesis at least in part because of a role in adhesion between the contractile ring and the plasma membrane...
  80. ncbi Inhibition of mTORC1 leads to MAPK pathway activation through a PI3K-dependent feedback loop in human cancer
    Arkaitz Carracedo
    Cancer Genetics Program, Beth Israel Deaconess Cancer Center, Harvard Medical School, Boston, Massachusetts, USA
    J Clin Invest 118:3065-74. 2008
    ....
  81. ncbi Molecular balance between the regulatory and catalytic subunits of phosphoinositide 3-kinase regulates cell signaling and survival
    Kohjiro Ueki
    Research Division, Joslin Diabetes Center, Harvard Medical School Division of Signal Transduction, Beth Israel Deaconess Medical Center, Boston, Massachusetts, USA
    Mol Cell Biol 22:965-77. 2002
    ..Thus, a reduction in p85alpha represents a novel therapeutic target for enhancing IGF-1/insulin signaling, prolongation of cell survival, and protection against apoptosis...
  82. ncbi Positive and negative roles of p85 alpha and p85 beta regulatory subunits of phosphoinositide 3-kinase in insulin signaling
    Kohjiro Ueki
    Research Division, Joslin Diabetes Center and Harvard Medical School, Boston, Massachusetts 02215, USA
    J Biol Chem 278:48453-66. 2003
    ..Thus, p85 alpha and p85 beta modulate PI 3-kinase-dependent signaling by multiple mechanisms and transmit signals independent of PI 3-kinase activation...
  83. ncbi Reduced expression of the murine p85alpha subunit of phosphoinositide 3-kinase improves insulin signaling and ameliorates diabetes
    Franck Mauvais-Jarvis
    Research Division, Joslin Diabetes Center and Department of Medicine, Harvard Medical School, Boston, Massachusetts 02115, USA
    J Clin Invest 109:141-9. 2002
    ..Furthermore, Pik3r1 heterozygosity protects mice with genetic insulin resistance from developing diabetes. These data suggest that regulation of p85alpha levels may provide a novel therapeutic target for the treatment of type 2 diabetes...
  84. ncbi The PHD finger of the chromatin-associated protein ING2 functions as a nuclear phosphoinositide receptor
    Or Gozani
    Department of Cell Biology, Harvard Medical School, Boston, MA 02115, USA
    Cell 114:99-111. 2003
    ..Together, our data identify the PHD finger as a phosphoinositide binding module and a nuclear PtdInsP receptor, and suggest that PHD-phosphoinositide interactions directly regulate nuclear responses to DNA damage...
  85. ncbi A rapid method for determining protein kinase phosphorylation specificity
    Jessica E Hutti
    Division of Signal Transduction, Harvard Medical School, 330 Brookline Avenue, Boston, Massachusetts 02215, USA
    Nat Methods 1:27-9. 2004
    ..Here we describe a combinatorial peptide library method that allows rapid generation of phosphorylation motifs for serine/threonine kinases...
  86. ncbi Modulation of epithelial neoplasia and lymphoid hyperplasia in PTEN+/- mice by the p85 regulatory subunits of phosphoinositide 3-kinase
    Ji Luo
    Division of Signal Transduction, Beth Israel Deaconess Medical Center and Department of Systems Biology, Harvard Medical School, Boston, MA 02115, USA
    Proc Natl Acad Sci U S A 102:10238-43. 2005
    ....
  87. ncbi The Mycobacterium tuberculosis serine/threonine kinases PknA and PknB: substrate identification and regulation of cell shape
    Choong Min Kang
    Division of Infectious Diseases, Children s Hospital Boston, Harvard Medical School, Boston, Massachusetts 02115, USA
    Genes Dev 19:1692-704. 2005
    ..These data indicate that signal transduction mediated by these kinases is a novel mechanism for the regulation of cell shape in mycobacteria, one that may be conserved among gram-positive bacteria...
  88. ncbi The Peutz-Jegher gene product LKB1 is a mediator of p53-dependent cell death
    P Karuman
    Department of Cell Biology, Harvard Medical School, 02115, Boston, MA, USA
    Mol Cell 7:1307-19. 2001
    ..We propose that a deficiency in apoptosis is a key factor in the formation of multiple benign intestinal polyps in PJS patients, and possibly for the subsequent development of malignant tumors in these patients...
  89. ncbi In vivo near-infrared fluorescence imaging of osteoblastic activity
    A Zaheer
    Department of Radiology, Beth Israel Deaconess Medical Center, Boston, MA 02215, USA
    Nat Biotechnol 19:1148-54. 2001
    ....
  90. ncbi Phosphoinositide 3-kinase binds constitutively to alpha/beta-tubulin and binds to gamma-tubulin in response to insulin
    R Kapeller
    Department of Medicine, Beth Israel Hospital, Boston, Massachusetts 02215, USA
    J Biol Chem 270:25985-91. 1995
    ..These data suggest that phosphoinositide 3-kinase may be involved in regulating microtubule responses to insulin and platelet-derived growth factor...
  91. ncbi Prognostic significance of AMP-activated protein kinase expression and modifying effect of MAPK3/1 in colorectal cancer
    Y Baba
    Department of Medical Oncology, Dana Farber Cancer Institute and Harvard Medical School, 44 Binney Street, Room JF 215C, Boston, MA 02115, USA
    Br J Cancer 103:1025-33. 2010
    ..AMP-activated protein kinase activation is cytotoxic to cancer cells, supporting AMPK as a tumour suppressor and a potential therapeutic target. However, no study has examined its prognostic role in colorectal cancers...
  92. ncbi The negative regulation of phosphoinositide 3-kinase signaling by p85 and it's implication in cancer
    Ji Luo
    Department of Systems Biology, Harvard Medical School and Division of Signal Transduction, Beth Israel Deaconess Medical Center, Boston, Massachusetts 02115, USA
    Cell Cycle 4:1309-12. 2005
    ..These findings lend new insight to how changes in p85 gene dosage or mutations in p85 could lead to the hyper-activation of PI3K and thus contribute towards tumorigenesis...
  93. ncbi Using peptide libraries to identify optimal cleavage motifs for proteolytic enzymes
    Benjamin E Turk
    Division of Signal Transduction, Beth Israel Deaconess Medical Center, Department of Cell Biology, Harvard Medical School, 330 Brookline Avenue, Boston, MA 02215, USA
    Methods 32:398-405. 2004
    ..Here, we describe in detail methodology that allows for the rapid and general determination of optimal recognition sequences for proteolytic enzymes...
  94. ncbi Novel PI 3-kinase-dependent mechanisms of trypanosome invasion and vacuole maturation
    Aaron M Woolsey
    Department of Immunology and Infectious Diseases, Harvard School of Public Health, Boston, MA 02115, USA
    J Cell Sci 116:3611-22. 2003
    ..Jointly, these data provide a new paradigm for T. cruzi invasion of non-professional phagocytic cells and reveal a novel vacuole maturation process that appears to bypass the requirement for EEA1...
  95. ncbi Akt/protein kinase B promotes organ growth in transgenic mice
    Tetsuo Shioi
    Cardiovascular Division, Beth Israel Deaconess Medical Center, Boston, Massachusetts 02215, USA
    Mol Cell Biol 22:2799-809. 2002
    ..In conclusion, Akt is sufficient to induce a marked increase in heart size and is likely to be one of the effectors of the PI3K pathway in mediating heart growth...
  96. ncbi The Crohn's disease protein, NOD2, requires RIP2 in order to induce ubiquitinylation of a novel site on NEMO
    Derek W Abbott
    Division of Gastrointestinal Pathology, Department of Pathology, Brigham and Women s Hospital, Harvard Medical School, Boston, MA, USA
    Curr Biol 14:2217-27. 2004
    ..NOD2 can both strongly activate and negatively attenuate NF-kB signaling. The biochemical mechanism for this dual function of NOD2 is unknown...
  97. ncbi The p85 regulatory subunit of phosphoinositide 3-kinase down-regulates IRS-1 signaling via the formation of a sequestration complex
    Ji Luo
    Department of Systems Biology, Harvard Medical School, Beth Israel Deaconess Medical Center, Boston, MA 02115, USA
    J Cell Biol 170:455-64. 2005
    ..These results suggest a mechanism of signal down-regulation of IRS-1 that is mediated by monomeric p85 through the formation of a sequestration complex between p85 and IRS-1...
  98. ncbi Glucose addiction of TSC null cells is caused by failed mTORC1-dependent balancing of metabolic demand with supply
    Andrew Y Choo
    Department of Cell Biology, Harvard Medical School, Boston, MA 02115, USA
    Mol Cell 38:487-99. 2010
    ..Therefore, mTORC1 inhibition during energetic stress is primarily to balance metabolic demand with supply...
  99. ncbi Phosphoinositide 3-kinase regulatory subunit p85alpha suppresses insulin action via positive regulation of PTEN
    Cullen M Taniguchi
    Cellular and Molecular Physiology, Joslin Diabetes Center, Harvard Medical School, Boston, MA 02215, USA
    Proc Natl Acad Sci U S A 103:12093-7. 2006
    ..Thus, the regulatory subunit p85alpha is a critical modulator of insulin sensitivity in vivo not only because of its effects on PI3K activation, but also as a regulator of PTEN activity...
  100. ncbi Targeting a common collaborator in cancer development
    Andrea P Myers
    Division of Women s Cancers, Department of Medical Oncology, Dana Farber Cancer Institute, Boston, MA 02115, USA
    Sci Transl Med 2:48ps45. 2010
    ..Here, we discuss the potential implications of these data on the clinical development of PI3K pathway inhibitors as cancer therapeutics...
  101. ncbi The role of phosphoinositide 3-kinase in human disease
    Lewis C Cantley
    Division of Signal Transduction, Beth Israel Deaconess Medical Center and Department of Systems Biology, Harvard Medical School, Boston, Massachusetts, USA
    Harvey Lect 100:103-22. 2004