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Neutrophil activation by fMLP regulates FOXO (forkhead) transcription factors by multiple pathways, one of which includes the binding of FOXO to the survival factor Mcl‐1
Author(s) -
Crossley Lisa J.
Publication year - 2003
Publication title -
journal of leukocyte biology
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.819
H-Index - 191
eISSN - 1938-3673
pISSN - 0741-5400
DOI - 10.1189/jlb.0103020
Subject(s) - forkhead transcription factors , biology , transcription factor , foxo3 , foxo1 , kinase , protein kinase b , microbiology and biotechnology , phosphorylation , proto oncogene proteins c akt , chemotaxis , biochemistry , receptor , gene
Activation signals from bacterial stimuli set into motion a series of events that alter the abbreviated lifespan of neutrophils. These studies show that the bacterial chemoattractant, formyl‐Met‐Leu‐Phe (fMLP), promotes the phosphorylation/inactivation of the FOXO subfamily of forkhead transcription factors (FKHR, FKHR‐L1, and AFX) through the phosphatidylinositol‐3‐kinase/Akt (protein kinase B) and the RAS mitogen‐activated protein kinase pathways. Furthermore, fMLP stimulation causes the inducible expression of the prosurvival Bcl‐2 family member Mcl‐1, which then binds to a complex containing FKHR. These studies show that fMLP‐stimulated neutrophils coordinate the regulation of FOXO transcription factors and the survival factor Mcl‐1, a mechanism that may allow neutrophils to alter their survival.