Ral is both necessary and sufficient for the inhibition of myeloid differentiation mediated by Ras.

Molecular and Cellular Biology
Nader OmidvarRichard L Darley

Abstract

Hyperactivation of Ras is one of the most common abnormalities in acute myeloid leukemia. In experimental models, Ras inhibits myeloid differentiation, which is characteristic of leukemia; however, the mechanism through which it disrupts hematopoiesis is poorly understood. In multipotent FDCP-mix cells, Ras inhibits terminal neutrophil differentiation, thereby indefinitely extending their proliferative potential. Ras also strongly promotes the sensitivity of these cells to granulocyte-macrophage colony-stimulating factor (GM-CSF). Using this model, we have dissected the signaling elements downstream of Ras to determine their relative contribution to the dysregulation of hematopoiesis. Cells expressing Ras mutants selectively activating Raf (Ras*T35S) or phosphatidylinositol 3-kinase (Ras*Y40C) did not significantly affect differentiation or proliferative capacity, whereas Ras*E37G (which selectively activates RalGEFs) perpetuated proliferation and blocked neutrophil development in a manner similar to that of Ras. Correspondingly, expression of constitutively active versions of these effectors confirmed the overriding importance of Ral guanine nucleotide exchange factors. Cells expressing Ras demonstrated hyperactivation of Ral,...Continue Reading

References

Dec 1, 1990·The American Review of Respiratory Disease·S Rodenhuis, R J Slebos
Dec 1, 1987·Proceedings of the National Academy of Sciences of the United States of America·J W JanssenC R Bartram
Mar 1, 1988·Proceedings of the National Academy of Sciences of the United States of America·C J FarrC J Marshall
Jun 1, 1995·The Journal of Experimental Medicine·K W MuszynskiJ R Keller
Sep 22, 1995·The Journal of Biological Chemistry·V Jullien-FloresJ H Camonis
Dec 16, 1993·Nature·M S Boguski, F McCormick
Jul 12, 1996·The Journal of Biological Chemistry·M A WhiteM H Wigler
Apr 1, 1996·Current Opinion in Cell Biology·C J Marshall
Nov 1, 1996·Trends in Biochemical Sciences·L A FeigS Cantor
Nov 22, 1997·Current Biology : CB·R LinD Manor
May 5, 1998·Molecular and Cellular Biology·R M WolthuisJ L Bos
Jul 1, 1998·International Reviews of Immunology·W S Alexander
Dec 5, 1998·Oncogene·T Matsuguchi, A S Kraft
Mar 2, 1999·Biochemical and Biophysical Research Communications·P FrankelD A Foster
Mar 3, 1999·Proceedings of the National Academy of Sciences of the United States of America·Y OhtaT P Stossel
Jun 22, 1999·The Journal of Biological Chemistry·X Zou, K Calame
Jul 15, 1999·The New England Journal of Medicine·S FaderlH M Kantarjian
Aug 7, 1999·The Journal of Biological Chemistry·R LinD Manor
Oct 6, 1999·Current Biology : CB·I VästrikP Doherty
Oct 7, 2000·The Journal of Biological Chemistry·C SongT Kataoka
Feb 17, 2001·The EMBO Journal·G G KelleyA V Smrcka
May 23, 2001·Current Biology : CB·P J Cullen
Dec 12, 2001·Nature Cell Biology·Serge MoskalenkoMichael A White
Feb 19, 2002·British Journal of Haematology·Mohammad Reza Ahmadian

❮ Previous
Next ❯

Citations

Nov 23, 2013·Frontiers of Medicine·Jessica Fredericks, Ruibao Ren
Mar 1, 1996·Trends in Neurosciences·C Charriaut-MarlangueY Ben-Ari
Feb 13, 2008·Molecular and Cellular Biology·Margaret P QuinlanJeffrey Settleman
Jul 23, 2011·Genes & Cancer·Stephan GysinFrank McCormick
Jan 28, 2009·The Journal of Cell Biology·Sharon DewittMaurice B Hallett
Mar 17, 2009·Journal of Neurochemistry·Milan MakwanaGenndij Raivich
Oct 20, 2017·Cancer Medicine·Adel Rezaei MoghadamFaris Farassati
Apr 23, 2009·Journal of Cell Science·Giovanna Lalli
May 19, 2010·Cellular Signalling·Elisa Ferro, Lorenza Trabalzini

❮ Previous
Next ❯

Related Concepts

Related Feeds

AML: Role of LSD1 by CRISPR (Keystone)

Find the latest rersearrch on the ability of CRISPR-Cas9 mutagenesis to profile the interactions between lysine-specific histone demethylase 1 (LSD1) and chemical inhibitors in the context of acute myeloid leukemia (AML) here.

Allergy and Asthma

Allergy and asthma are inflammatory disorders that are triggered by the activation of an allergen-specific regulatory t cell. These t cells become activated when allergens are recognized by allergen-presenting cells. Here is the latest research on allergy and asthma.

AKT Pathway

This feed focuses on the AKT serine/threonine kinase, which is an important signaling pathway involved in processes such as glucose metabolism and cell survival.

Acute Myeloid Leukemia

Acute myeloid leukemia (AML) is a clinically and genetically heterogeneous disease with approximately 20,000 cases per year in the United States. AML also accounts for 15-20% of all childhood acute leukemias, while it is responsible for more than half of the leukemic deaths in these patients. Here is the latest research on this disease.