NADPH oxidases regulate cell growth and migration in myeloid cells transformed by oncogenic tyrosine kinases

Transformation by tyrosine kinase oncogenes in myeloid malignancies, including BCR-ABL in chronic myeloid leukemia, FLT3ITD in acute myeloid leukemia (AML) or JAK2V617F in myeloproliferative neoplasms (MPN), is associated with increased growth and cytoskeletal abnormalities. Using targeted approache...

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Main Authors:	Reddy, Mamatha M., Fernandes, Margret S., Salgia, Ravi, Levine, Ross L., Griffin, James D., Sattler, Martin
Format:	Online
Language:	English
Published:	2010
Online Access:	https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4078661/

id	pubmed-4078661
recordtype	oai_dc
spelling	pubmed-40786612014-07-02 NADPH oxidases regulate cell growth and migration in myeloid cells transformed by oncogenic tyrosine kinases Reddy, Mamatha M. Fernandes, Margret S. Salgia, Ravi Levine, Ross L. Griffin, James D. Sattler, Martin Article Transformation by tyrosine kinase oncogenes in myeloid malignancies, including BCR-ABL in chronic myeloid leukemia, FLT3ITD in acute myeloid leukemia (AML) or JAK2V617F in myeloproliferative neoplasms (MPN), is associated with increased growth and cytoskeletal abnormalities. Using targeted approaches against components of the superoxide-producing NADPH-oxidases, including NOX2, NOX4 and the common p22phox subunit of NOX1-4, myeloid cells were found to display reduced cell growth and spontaneous migration. Consistent with a role of NOX as regulators of membrane proximal signaling events in non-phagocytic cells, NOX2 and NOX4 were not involved in the excess production of intracellular reactive oxygen species and did not significantly increase oxygen consumption. All NOX family members are controlled in part through levels of the rate-limiting substrate NADPH, which was found to be significantly elevated in tyrosine kinase oncogene transformed cells. Also, reduced phosphorylation of the actin filament crosslinking protein MARCKS in response to suppression of p22phox hints at a novel effector of NOX signaling. MARCKS was also found to be required for increased migration. Overall, these data suggest a model whereby NOX links metabolic NADPH production to cellular events that directly contribute to transformation. 2010-11-12 2011-02 /pmc/articles/PMC4078661/ /pubmed/21072051 http://dx.doi.org/10.1038/leu.2010.263 Text en Users may view, print, copy, download and text and data- mine the content in such documents, for the purposes of academic research, subject always to the full Conditions of use: http://www.nature.com/authors/editorial_policies/license.html#terms
repository_type	Open Access Journal
institution_category	Foreign Institution
institution	US National Center for Biotechnology Information
building	NCBI PubMed
collection	Online Access
language	English
format	Online
author	Reddy, Mamatha M. Fernandes, Margret S. Salgia, Ravi Levine, Ross L. Griffin, James D. Sattler, Martin
spellingShingle	Reddy, Mamatha M. Fernandes, Margret S. Salgia, Ravi Levine, Ross L. Griffin, James D. Sattler, Martin NADPH oxidases regulate cell growth and migration in myeloid cells transformed by oncogenic tyrosine kinases
author_facet	Reddy, Mamatha M. Fernandes, Margret S. Salgia, Ravi Levine, Ross L. Griffin, James D. Sattler, Martin
author_sort	Reddy, Mamatha M.
title	NADPH oxidases regulate cell growth and migration in myeloid cells transformed by oncogenic tyrosine kinases
title_short	NADPH oxidases regulate cell growth and migration in myeloid cells transformed by oncogenic tyrosine kinases
title_full	NADPH oxidases regulate cell growth and migration in myeloid cells transformed by oncogenic tyrosine kinases
title_fullStr	NADPH oxidases regulate cell growth and migration in myeloid cells transformed by oncogenic tyrosine kinases
title_full_unstemmed	NADPH oxidases regulate cell growth and migration in myeloid cells transformed by oncogenic tyrosine kinases
title_sort	nadph oxidases regulate cell growth and migration in myeloid cells transformed by oncogenic tyrosine kinases
description	Transformation by tyrosine kinase oncogenes in myeloid malignancies, including BCR-ABL in chronic myeloid leukemia, FLT3ITD in acute myeloid leukemia (AML) or JAK2V617F in myeloproliferative neoplasms (MPN), is associated with increased growth and cytoskeletal abnormalities. Using targeted approaches against components of the superoxide-producing NADPH-oxidases, including NOX2, NOX4 and the common p22phox subunit of NOX1-4, myeloid cells were found to display reduced cell growth and spontaneous migration. Consistent with a role of NOX as regulators of membrane proximal signaling events in non-phagocytic cells, NOX2 and NOX4 were not involved in the excess production of intracellular reactive oxygen species and did not significantly increase oxygen consumption. All NOX family members are controlled in part through levels of the rate-limiting substrate NADPH, which was found to be significantly elevated in tyrosine kinase oncogene transformed cells. Also, reduced phosphorylation of the actin filament crosslinking protein MARCKS in response to suppression of p22phox hints at a novel effector of NOX signaling. MARCKS was also found to be required for increased migration. Overall, these data suggest a model whereby NOX links metabolic NADPH production to cellular events that directly contribute to transformation.
publishDate	2010
url	https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4078661/
_version_	1612108887841832960

NADPH oxidases regulate cell growth and migration in myeloid cells transformed by oncogenic tyrosine kinases

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