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Activation of a Rel‐A/CEBP‐β‐related transcription factor heteromer by PGG‐Glucan in a murine monocytic cell line
Author(s) -
Adams David S.,
Nathans Robin,
Pero Stephanie C.,
Sen Ami,
Wakshull Eric
Publication year - 2000
Publication title -
journal of cellular biochemistry
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.028
H-Index - 165
eISSN - 1097-4644
pISSN - 0730-2312
DOI - 10.1002/(sici)1097-4644(20000501)77:2<221::aid-jcb6>3.0.co;2-v
Subject(s) - transcription factor , signal transduction , protein kinase a , biology , microbiology and biotechnology , chemistry , biochemistry , kinase , gene
PGG‐Glucan is a soluble β‐glucan immunomodulator that enhances a variety of leukocyte microbicidal activities without activating inflammatory cytokines. Although several different cell surface receptors for soluble (and particulate) β‐glucans have been described, the signal transduction pathway(s) used by these soluble ligands have not been elucidated. Previously we reported that PGG‐Glucan treatment of mouse BMC2.3 macrophage cells activates a nuclear factor κ‐B‐like (NF‐κB) transcription factor complex containing subunit p65 (rel‐A) attached to an unidentified cohort. In this study, we identify the cohort to be a non‐rel family member: a CCAAT enhancer‐binding protein‐β (C/EBP‐β)‐related molecule with an apparent size of 48 kDa, which is a different protein than the previously identified C/EBP‐β p34 also present in these cells. C/EBP‐β is a member of the bZIP family whose members have previously been shown to interact with rel family members. This rel/bZIP heteromer complex activated by PGG‐Glucan is different from the p65/p50 rel/rel complex induced in these cells by lipopolysaccharide (LPS). Thus, our data demonstrate that PGG‐Glucan uses signal transduction pathways different from those used by LPS, which activates leukocyte microbicidal activities and inflammatory cytokines. We further show that heteromer activation appears to use protein kinase C (PKC) and protein tyrosine kinase (PTK) pathways, but not mitogen‐activated protein kinase p38. Inhibitor κ‐B‐α (IκB‐α) is associated with the heteromer; this association decreases after PGG‐Glucan treatment. These data are consistent with a model whereby treatment of BMC2.3 cells with PGG‐Glucan activates IκB‐α via PKC and/or PTK pathways, permitting translocation of the rel‐A/CEBP‐β heteromer complex to the nucleus and increases its DNA‐binding affinity. J. Cell. Biochem. 77:221–233, 2000. © 2000 Wiley‐Liss, Inc.