Transgenic expression of numb inhibits notch signaling in immature thymocytes but does not alter T cell fate specification

The Journal of Immunology : Official Journal of the American Association of Immunologists
Michelle B FrenchC Jane McGlade

Abstract

The conserved adaptor protein Numb is an intrinsic cell fate determinant that functions by antagonizing Notch-mediated signal transduction. The Notch family of membrane receptors controls cell survival and cell fate determination in a variety of organ systems and species. Recent studies have identified a role for mammalian Notch-1 signals at multiple stages of T lymphocyte development. We have examined the role of mammalian Numb (mNumb) as a Notch regulator and cell fate determinant during T cell development. Transgenic overexpression of mNumb under the control of the Lck proximal promoter reduced expression of several Notch-1 target genes, indicating that mNumb antagonizes Notch-1 signaling in vivo. However, thymocyte development, cell cycle, and survival were unperturbed by mNumb overexpression, even though transgenic Numb was expressed at an early stage in thymocyte development (CD4(-)CD8(-)CD3(-) cells that were CD44(+)CD25(+) or CD44(-)CD25(+); double-negative 2/3). Moreover, bone marrow from mNumb transgenic mice showed no defects in thymopoiesis in competitive repopulation experiments. Our results suggest that mNumb functions as a Notch-1 antagonist in immature thymocytes, but that suppression of Notch-1 signaling at thi...Continue Reading

References

Aug 1, 1988·Molecular and Cellular Biology·A M GarvinR M Perlmutter
Mar 10, 1995·Cell·P Bork, B Margolis
Apr 1, 1996·Current Opinion in Immunology·J C Zúñiga-Pflücker, M J Lenardo
Oct 15, 1996·Proceedings of the National Academy of Sciences of the United States of America·E FriseY N Jan
Nov 25, 1996·Developmental Biology·C ShawberG Weinmaster
Oct 29, 1997·Molecular and Cellular Biology·A J CapobiancoJ M Bishop
Jun 25, 1998·Molecular and Cellular Biology·T Juven-GershonM Oren
Jan 9, 1999·Immunity·M L DeftosM J Bevan
Apr 30, 1999·Science·S Artavanis-TsakonasR J Lake
May 14, 1999·Genes & Development·K TomitaR Kageyama
Sep 1, 1999·Proceedings of the National Academy of Sciences of the United States of America·J M VerdiH D Lipshitz
Jan 8, 2000·Immunity·B Osborne, L Miele
Jun 7, 2000·Proceedings of the National Academy of Sciences of the United States of America·W ZhongY N Jan
Dec 21, 2000·The Journal of Cell Biology·E SantoliniP P Di Fiore
Jun 20, 2001·Current Biology : CB·O ZilianM Aguet

❮ Previous
Next ❯

Citations

Oct 9, 2002·Immunological Reviews·David AllmanWarren S Pear
May 22, 2007·The Journal of Immunology : Official Journal of the American Association of Immunologists·Anne WilsonOlav Zilian
Apr 5, 2016·Oncogene·D RajendranC J McGlade
Apr 12, 2003·Current Opinion in Hematology·Hongfang Wang, Gerald J Spangrude
Nov 26, 2002·Immunological Reviews·Jun HirosePaul W Kincade
Feb 27, 2004·Nature Immunology·Freddy RadtkeH Robson MacDonald
Mar 18, 2005·Annual Review of Immunology·Ivan MaillardWarren S Pear
Oct 21, 2005·BioEssays : News and Reviews in Molecular, Cellular and Developmental Biology·Freddy RadtkeH Robson MacDonald
Feb 2, 2006·Immunological Reviews·Ioana VisanCynthia J Guidos
Mar 3, 2010·Annual Review of Immunology·Julie S YuanCynthia J Guidos
Sep 10, 2004·The Journal of Immunology : Official Journal of the American Association of Immunologists·Sonja HöflingerMeinrad Busslinger
Jun 10, 2005·The Journal of Immunology : Official Journal of the American Association of Immunologists·Jens van den BrandtHolger M Reichardt
Feb 2, 2006·Immunological Reviews·Karen LakyB J Fowlkes
Oct 17, 2014·Cell Death & Disease·N M Martin-BlancoI Screpanti
Dec 23, 2017·The Journal of Cell Biology·Ivan Nicola ColalucaPier Paolo Di Fiore
Aug 19, 2007·The Journal of Experimental Medicine·Karen Laky, B J Fowlkes
May 25, 2004·Molecular Biology of the Cell·Christian A SmithC Jane McGlade
Apr 28, 2009·Development·Lily L Wong, David H Rapaport
Nov 30, 2002·Seminars in Immunology·Cynthia J Guidos
Apr 12, 2003·Seminars in Immunology·Ute KochCynthia J Guidos
Mar 17, 2004·Current Opinion in Immunology·Freddy RadtkeH Robson MacDonald
May 12, 2004·Current Opinion in Immunology·Ellen A Robey, Jeffery A Bluestone
Jun 23, 2009·Differentiation; Research in Biological Diversity·Laura GrisantiElena Vicini

❮ Previous
Next ❯

Related Concepts

Related Feeds

Cell Fate Specification

Cell fate specification is determined by complex signal transduction pathways including Notch and the Sonic hedgehog signaling pathway. Here is the latest research on regulation of cell fate determination.