Abstract
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.
Publication types
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Research Support, U.S. Gov't, P.H.S.
MeSH terms
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Animals
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Cell Cycle Proteins
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DNA-Binding Proteins / metabolism*
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Forkhead Box Protein O1
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Forkhead Transcription Factors
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Guinea Pigs
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Humans
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Mitogen-Activated Protein Kinases / physiology
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Myeloid Cell Leukemia Sequence 1 Protein
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N-Formylmethionine Leucyl-Phenylalanine / pharmacology*
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Neoplasm Proteins / metabolism*
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Neutrophil Activation / drug effects*
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Neutrophils / metabolism*
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Phosphatidylinositol 3-Kinases / physiology
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Phosphorylation
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Protein Serine-Threonine Kinases*
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Proto-Oncogene Proteins / metabolism
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Proto-Oncogene Proteins c-akt
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Proto-Oncogene Proteins c-bcl-2*
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Ribosomal Protein S6 Kinases, 90-kDa / physiology
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Transcription Factors / metabolism*
Substances
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Cell Cycle Proteins
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DNA-Binding Proteins
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FOXO1 protein, human
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FOXO4 protein, human
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Forkhead Box Protein O1
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Forkhead Transcription Factors
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Myeloid Cell Leukemia Sequence 1 Protein
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Neoplasm Proteins
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Proto-Oncogene Proteins
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Proto-Oncogene Proteins c-bcl-2
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Transcription Factors
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N-Formylmethionine Leucyl-Phenylalanine
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AKT1 protein, human
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Protein Serine-Threonine Kinases
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Proto-Oncogene Proteins c-akt
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Ribosomal Protein S6 Kinases, 90-kDa
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ribosomal protein S6 kinase, 90kDa, polypeptide 3
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Mitogen-Activated Protein Kinases