Interleukin-4 is a multifunctional cytokine that plays a critical role in the regulation of immun... more Interleukin-4 is a multifunctional cytokine that plays a critical role in the regulation of immune responses. Its effects depend upon binding to and signaling through a receptor complex consisting of the IL-4R alpha chain and the common gamma chain (gamma c), resulting in a series of phosphorylation events mediated by receptor-associated kinases. In turn, these cause the recruitment of mediators of cell growth, of resistance to apoptosis, and of gene activation and differentiation. Here we describe our current understanding of the organization of the IL-4 receptor, of the signaling pathways that are induced as a result of receptor occupancy, and of the various mechanisms through which receptor function is modulated. We particularly emphasize the modular nature of the receptor and the specialization of different receptor regions for distinct functions, most notably the independent regulation of cell growth and gene activation.
The PTEN gene encodes a 403-amino-acid polypeptide with a high degree of homology to protein tyro... more The PTEN gene encodes a 403-amino-acid polypeptide with a high degree of homology to protein tyrosine phosphatases and tensin Steck et al., ‡ synthetic substrates in vitro (Myers et al., 1997). Re-* Amgen Institute cent evidence also demonstrates the ability of PTEN 620 University Avenue to dephosphorylate position D3 of phosphatidylinositol Toronto, Ontario (3,4,5) trisphosphate, a direct product of phosphatidyl- † Ontario Cancer Institute and Departments inositol 3Ј kinase (PI3ЈK) activity (Maehama and Dixon, of Medical Biophysics and Immunology 1998). The importance of an intact PTEN phosphatase University of Toronto domain for its tumor suppressor function is underscored Toronto, Ontario by findings that a large proportion of tumor-associated Canada M5G 2C1 PTEN mutations map to the region encoding the phosphatase domain (Rasheed et al., 1997; Marsh et al., 1998). Furthermore, unlike wild-type PTEN, catalytically Summary inactive PTEN is unable to suppress growth and tumorigenicity of PTEN-deficient glioblastoma cells (Furnari et PTEN is a tumor suppressor with sequence homology al. , 1997).
Polymerase chain reaction (PCR) is a technique widely used in fungal research. One of its advanta... more Polymerase chain reaction (PCR) is a technique widely used in fungal research. One of its advantages is the ability to amplify very small amounts of DNA, in the picograms range, even in
TRAF2 is an intracellular signal-transducing protein recruited to the TNFR1 and TNFR2 receptors f... more TRAF2 is an intracellular signal-transducing protein recruited to the TNFR1 and TNFR2 receptors following TNF stimulation. To investigate the physiological role of TRAF2, we generated TRAF2-deficient mice. traf2-/- mice appeared normal at birth but became progressively runted and died prematurely. Atrophy of the thymus and spleen and depletion of B cell precursors also were observed. Thymocytes and other hematopoietic progenitors were highly sensitive to TNF-induced cell death and serum TNF levels were elevated in these TRAF2-deficient animals. Examination of traf2-/- cells revealed a severe reduction in TNF-mediated JNK/SAPK activation but a mild effect on NF-kappaB activation. These results suggest that TRAF2-independent pathways of NF-kappaB activation exist and that TRAF2 is required for an NF-kappaB-independent signal that protects against TNF-induced apoptosis.
Corrigendum to:'ACC/AHA/ESC 2006 guidelines for the management of patients with atri... more Corrigendum to:'ACC/AHA/ESC 2006 guidelines for the management of patients with atrial fibrillation–executive summary. A report of the American College of Cardiology/American Heart Association Task Force on practice guidelines and the European…
Interleukin-4 is a multifunctional cytokine that plays a critical role in the regulation of immun... more Interleukin-4 is a multifunctional cytokine that plays a critical role in the regulation of immune responses. Its effects depend upon binding to and signaling through a receptor complex consisting of the IL-4R alpha chain and the common gamma chain (gamma c), resulting in a series of phosphorylation events mediated by receptor-associated kinases. In turn, these cause the recruitment of mediators of cell growth, of resistance to apoptosis, and of gene activation and differentiation. Here we describe our current understanding of the organization of the IL-4 receptor, of the signaling pathways that are induced as a result of receptor occupancy, and of the various mechanisms through which receptor function is modulated. We particularly emphasize the modular nature of the receptor and the specialization of different receptor regions for distinct functions, most notably the independent regulation of cell growth and gene activation.
The PTEN gene encodes a 403-amino-acid polypeptide with a high degree of homology to protein tyro... more The PTEN gene encodes a 403-amino-acid polypeptide with a high degree of homology to protein tyrosine phosphatases and tensin Steck et al., ‡ synthetic substrates in vitro (Myers et al., 1997). Re-* Amgen Institute cent evidence also demonstrates the ability of PTEN 620 University Avenue to dephosphorylate position D3 of phosphatidylinositol Toronto, Ontario (3,4,5) trisphosphate, a direct product of phosphatidyl- † Ontario Cancer Institute and Departments inositol 3Ј kinase (PI3ЈK) activity (Maehama and Dixon, of Medical Biophysics and Immunology 1998). The importance of an intact PTEN phosphatase University of Toronto domain for its tumor suppressor function is underscored Toronto, Ontario by findings that a large proportion of tumor-associated Canada M5G 2C1 PTEN mutations map to the region encoding the phosphatase domain (Rasheed et al., 1997; Marsh et al., 1998). Furthermore, unlike wild-type PTEN, catalytically Summary inactive PTEN is unable to suppress growth and tumorigenicity of PTEN-deficient glioblastoma cells (Furnari et PTEN is a tumor suppressor with sequence homology al. , 1997).
Polymerase chain reaction (PCR) is a technique widely used in fungal research. One of its advanta... more Polymerase chain reaction (PCR) is a technique widely used in fungal research. One of its advantages is the ability to amplify very small amounts of DNA, in the picograms range, even in
TRAF2 is an intracellular signal-transducing protein recruited to the TNFR1 and TNFR2 receptors f... more TRAF2 is an intracellular signal-transducing protein recruited to the TNFR1 and TNFR2 receptors following TNF stimulation. To investigate the physiological role of TRAF2, we generated TRAF2-deficient mice. traf2-/- mice appeared normal at birth but became progressively runted and died prematurely. Atrophy of the thymus and spleen and depletion of B cell precursors also were observed. Thymocytes and other hematopoietic progenitors were highly sensitive to TNF-induced cell death and serum TNF levels were elevated in these TRAF2-deficient animals. Examination of traf2-/- cells revealed a severe reduction in TNF-mediated JNK/SAPK activation but a mild effect on NF-kappaB activation. These results suggest that TRAF2-independent pathways of NF-kappaB activation exist and that TRAF2 is required for an NF-kappaB-independent signal that protects against TNF-induced apoptosis.
Corrigendum to:'ACC/AHA/ESC 2006 guidelines for the management of patients with atri... more Corrigendum to:'ACC/AHA/ESC 2006 guidelines for the management of patients with atrial fibrillation–executive summary. A report of the American College of Cardiology/American Heart Association Task Force on practice guidelines and the European…
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