Affiliation: University of Toronto
- The tumor suppressor activity of SOCS-1Robert Rottapel
Department of Immunology, University of Toronto, Canada
Oncogene 21:4351-62. 2002..These data suggest that loss-of-function of SOCS-1 may collaborate with a variety of hematopoietic oncogenes to facilitate tumor progression...
- Putting out the fire: coordinated suppression of the innate and adaptive immune systems by SOCS1 and SOCS3 proteinsIoannis D Dimitriou
Ontario Cancer Institute Toronto Medical Discovery Tower, Toronto, Canada
Immunol Rev 224:265-83. 2008..Thus, SOCS family proteins are components of an emerging immunoregulatory mechanism that maintains the coordinated balance of both innate and adaptive immune responses...
- CD28 regulates the translation of Bcl-xL via the phosphatidylinositol 3-kinase/mammalian target of rapamycin pathwayLinda X Wu
Department of Immunology, University of Toronto, Toronto, Ontario, Canada
J Immunol 174:180-94. 2005..These results demonstrate that CD28 relieves the translational inhibition of Bcl-x(L) in a PI3K/mammalian target of rapamycin-dependent manner...
- The RhoGEF GEF-H1 is required for oncogenic RAS signaling via KSR-1Jane Cullis
Princess Margaret Cancer Center, University Health Network, 101 College Street, Room 8 703, Toronto Medical Discovery Tower, University of Toronto, Toronto, ON M5G 1L7, Canada Department of Medical Biophysics, University of Toronto, 1 King s College Circle, Toronto, ON M5S 1A8, Canada
Cancer Cell 25:181-95. 2014..Our results, therefore, identify GEF-H1 as an amplifier of MAPK signaling and provide mechanistic insight into the progression of RAS mutant tumors. ..
- Survivin loss in thymocytes triggers p53-mediated growth arrest and p53-independent cell deathHitoshi Okada
Advanced Medical Discovery Institute, University of Toronto, 620 University Avenue, Suite 706, Ontario M5G 2C1, Canada
J Exp Med 199:399-410. 2004..Thus, survivin plays a critical role in early thymocyte development...
- Mechanistic insight into the microtubule and actin cytoskeleton coupling through dynein-dependent RhoGEF inhibitionDavid Meiri
Ontario Cancer Institute and The Campbell Family Cancer Research Institute, 101 College Street, Room 8 703 Toronto Medical Discovery Tower, University of Toronto, Toronto, ON M5G 1L7, Canada
Mol Cell 45:642-55. 2012..These studies demonstrate a pivotal role of Tctex-1 as a negative regulator of actin filament organization through its control of Lfc in the crosstalk between microtubule and actin cytoskeletons...
- Constitutive p38HOG mitogen-activated protein kinase activation induces permanent cell cycle arrest and senescenceRizwan Haq
Institute of Medical Science, University of Toronto, Ontario, Canada
Cancer Res 62:5076-82. 2002..These results define p38(HOG) as an intracellular pathway that activates a senescence checkpoint in tumor cells and may play a role in Ras- or stress-induced senescence...
- Homeodomain-interacting protein kinase (HIPK)-1 is required for splenic B cell homeostasis and optimal T-independent type 2 humoral responseFiona M Guerra
Department of Immunology, University of Toronto, Toronto, Ontario, Canada
PLoS ONE 7:e35533. 2012..Despite the expanded MZ B cell population in the HIPK1(-/-) mice, the T-independent type 2 humoral response was impaired. These data identify HIPK1 as a novel kinase required for optimal B cell function in mice...
- The 3BP2 adapter protein is required for chemoattractant-mediated neutrophil activationGrace Chen
Department of Immunology, University of Toronto, Toronto, Ontario M5S 148, Canada
J Immunol 189:2138-50. 2012..Our results reveal an obligate requirement for the adapter protein 3BP2 in G protein-coupled receptor-mediated neutrophil function...
- CD28-dependent activation of protein kinase B/Akt blocks Fas-mediated apoptosis by preventing death-inducing signaling complex assemblyRussell G Jones
Department of Medical Biophysics, Ontario Cancer Institute, University of Toronto, Canada
J Exp Med 196:335-48. 2002..These findings provide a novel link between CD28 and an important apoptosis pathway in vivo, and demonstrate that PI3K/PKB signaling prevents apoptosis by inhibiting DISC assembly...
- Immune functions in mice lacking Clnk, an SLP-76-related adaptor expressed in a subset of immune cellsOliver Utting
Laboratory of Molecular Oncology, Clinical Research Institute of Montreal, Montreal, Quebec, Canada H2W 1R7
Mol Cell Biol 24:6067-75. 2004..The results of our studies demonstrated that Clnk is dispensable for normal differentiation and function of T cells, mast cells, and NK cells. Hence, unlike its relatives, Clnk is not essential for normal immune functions...
- A positive regulatory role for suppressor of cytokine signaling 1 in IFN-gamma-induced MHC class II expression in fibroblastsSubburaj Ilangumaran
Ontario Cancer Institute, Toronto, Canada
J Immunol 169:5010-20. 2002....
- Suppressor of cytokine signaling 1 stringently regulates distinct functions of IL-7 and IL-15 in vivo during T lymphocyte development and homeostasisSheela Ramanathan
Immunology Division, Department of Pediatrics, Faculty of Medicine, University of Sherbrooke, Canada
J Immunol 176:4029-41. 2006..Our findings illustrate distinct functions for IL-7 and IL-15 in T lymphocyte development and homeostasis, and stringent regulation of these processes by SOCS1...
- Regulation of NF-kappaB signaling by Pin1-dependent prolyl isomerization and ubiquitin-mediated proteolysis of p65/RelAAkihide Ryo
Cancer Biology Program, Division of Hematology Oncology, Department of Medicine, Beth Israel Deaconess Medical Center, Harvard Medical School, 330 Brookline Avenue, HIM 1047, Boston, MA 02215, USA
Mol Cell 12:1413-26. 2003..These findings uncover two important mechanisms of regulating NF-kappaB signaling and offer new insight into the pathogenesis and treatment of some human diseases such as cancers...
- A novel SHP-1/Grb2-dependent mechanism of negative regulation of cytokine-receptor signaling: contribution of SHP-1 C-terminal tyrosines in cytokine signalingParham Minoo
Department of Medicine, Royal Victoria Hospital, McGill University, 687 Pine Ave West, Montreal, QC H3A 1A1, Canada
Blood 103:1398-407. 2004..All together, our results indicate that SHP-1 inhibits PRLR and EPOR signaling by recruitment and targeting of SOCS-1 to Jak2, highlighting a new mechanism of SHP-1 regulation of cytokine-receptor signaling...
- Regulation of cytokine receptor signaling by SOCS1Subburaj Ilangumaran
Ontario Cancer Institute, Princess Margaret Hospital, University Health Network, Toronto, Ontario, Canada
Immunol Rev 192:196-211. 2003....
- Autoinhibition of the kit receptor tyrosine kinase by the cytosolic juxtamembrane regionPerry M Chan
Division of Experimental Therapeutics, Ontario Cancer Institute, Princess Margaret Hospital, Toronto, Ontario M5G 2M9, Canada
Mol Cell Biol 23:3067-78. 2003....
- Signal transduction by several KIT juxtamembrane domain mutationsNathalie Casteran
Molecular and Functional Hematopoiesis Laboratory, U119 INSERM, 27 Bd Leï Roure 13009 Marseille, France
Oncogene 22:4710-22. 2003..We conclude that Kdelta27 is a new oncogenic KIT mutation showing constitutive activation of downstream signaling pathways, and suggest that specific pathways are activated by oncogenic KIT...
- Suppressor of cytokine signaling 1 attenuates IL-15 receptor signaling in CD8+ thymocytesSubburaj Ilangumaran
Rm 10 108, Ontario Cancer Institute, Princess Margaret Hospital, University Health Network, 610 University Ave, Toronto M5G 2M9, Canada
Blood 102:4115-22. 2003..Because many different cell types express IL-15, our results strongly suggest that SOCS1 functions as an indispensable attenuator of IL-15 receptor signaling in developing CD8+ thymocytes...
- Flow cytometric analysis of cytokine receptor signal transductionSubburaj Ilangumaran
Ontario Cancer Institute, Princess Margaret Hospital, University Health Network, 610 University Avenue, Toronto, ON, Canada M5G 2M9
J Immunol Methods 278:221-34. 2003..We envisage that this technique will find wide application in studying cytokine receptor signal transduction, particularly in identifying cytokine-dependent developmental checkpoints during hematopoiesis...
- Suppressor of cytokine signaling 1 regulates IL-15 receptor signaling in CD8+CD44high memory T lymphocytesSubburaj Ilangumaran
Ontario Cancer Institute, Princess Margaret Hospital, University Health Network, 610 University Avenue, Toronto, Ontario, Canada M5G 2M9
J Immunol 171:2435-45. 2003....
- Suppressor of cytokine signaling 1 regulates an endogenous inhibitor of a mast cell proteaseSubburaj Ilangumaran
Ontario Cancer Institute, Princess Margaret Hospital, University Health Network, 610 University Avenue, Toronto M5G 2M9, Canada
J Biol Chem 278:41871-80. 2003..These results show that SOCS1 is required for the expression and/or stability of an endogenous protease inhibitor, which protects mast cells from their own proteolytic enzymes...
- Regulation of the immune system by SOCS family adaptor proteinsSubburaj Ilangumaran
Faculty of Medicine, Immunology Division, University of Sherbrooke, 3001, 12th Avenue North, Sherbrooke, Que, Canada J1H 5N4
Semin Immunol 16:351-65. 2004..In this review, we will discuss the structure of SOCS proteins, mechanisms by which they control the JAK-STAT pathway and their role in immune regulation...
- The MAGUK family protein CARD11 is essential for lymphocyte activationHiromitsu Hara
Institute of Molecular Biotechnology of the Austrian Academy of Sciences, Dr Bohr Gasse 7, A 1030, Vienna, Austria
Immunity 18:763-75. 2003..Our results show that the same family of molecules are critical regulators of neuronal synapses and immune receptor signaling...
- CD28 provides T-cell costimulation and enhances PI3K activity at the immune synapse independently of its capacity to interact with the p85/p110 heterodimerFabien Garcon
Laboratory of Lymphocyte Signaling and Development, Babraham Institute, Babraham Research Campus, Cambridge, United Kingdom
Blood 111:1464-71. 2008..Consistent with this, CD28 and p110delta double-deficient mice were severely immune compromised. We therefore suggest that combined pharmaceutic targeting of p110delta activity and CD28 costimulation has potent therapeutic potential...
- The 3BP2 adapter protein is required for optimal B-cell activation and thymus-independent type 2 humoral responseGrace Chen
Princess Margaret Hospital Ontario Cancer Institute, Room 10 105, University Ave, Toronto, ON, Canada
Mol Cell Biol 27:3109-22. 2007..We show that 3BP2 binds via its SH2 domain to the CD19 signaling complex and is required for optimum Syk phosphorylation and calcium flux...
- Impaired V(D)J recombination and increased apoptosis among B cell precursors in the bone marrow of c-Abl-deficient miceQueenie Lai Kwan Lam
Department of Pathology and Center of Infection and Immunology, The University of Hong Kong, Hong Kong, China
Int Immunol 19:267-76. 2007..Taken together, we propose that c-Abl mediates a stage-specific anti-apoptotic response in precursor B cells and is required for efficient V(D)J recombination during B cell development...
- Ckap2 regulates aneuploidy, cell cycling, and cell death in a p53-dependent mannerKatsuya Tsuchihara
The Campbell Family Institute for Breast Cancer Research, Ontario Cancer Institute, Ontario, Canada
Cancer Res 65:6685-91. 2005..Our data suggest the existence of a functional positive feedback loop in which Ckap2 activates the G1 tetraploidy checkpoint and prevents aneuploidy...
- The Rho GTP exchange factor Lfc promotes spindle assembly in early mitosisChristopher J Bakal
Department of Medical Biophysics, University of Toronto, 1 King s College Circle, Toronto, ON, Canada M5S 1A8
Proc Natl Acad Sci U S A 102:9529-34. 2005..Lastly, we implicate mDia1 as an important effector of Lfc signaling. These findings demonstrate a role for Lfc, Rho, and mDia1 during mitosis...
- The molecular adapter Carma1 controls entry of IkappaB kinase into the central immune synapseHiromitsu Hara
IMBA, Institute of Molecular Biotechnology of the Austrian Academy of Sciences, c o Dr Bohr Gasse 3 5, A 1030 Vienna, Austria
J Exp Med 200:1167-77. 2004....