Induction of Mac-2BP by nerve growth factor is regulated by the PI3K/Akt/NF-kappaB-dependent pathway in the HEK293 cell line.

Stem Cell Research Center, KRIBB, Daejeon, Korea.
BMB reports (Impact Factor: 1.99). 12/2008; 41(11):784-9. DOI: 10.5483/BMBRep.2008.41.11.784
Source: PubMed

ABSTRACT Mac-2BP is a ligand of the galectin family that has been suggested to affect tumor proliferation and metastasis formation. We assessed Mac-2BP expression at the transcriptional and translational levels to evaluate nerve growth factor (NGF)-induced Mac-2BP expression. A time kinetic analysis using reverse transcription-polymerase chain reaction showed that NGF-induced Mac-2BP transcript levels were 4-5 times higher than in controls. Mac-2BP enzyme-linked immunosorbent assay and immunofluorescence staining showed a 2-3-fold increase in intracellular and secreted Mac-2BP as a result of NGF stimulation. This increase was regulated by Akt activation and NF-kappaB binding. p65 and p50-NF-kappaB are major transcriptional factors in the Mac-2BP promoter region, and were shown to be regulated in accordance with the Akt activation states. Collectively, these results suggest that NGF induces Mac-2BP expression via the PI3K/Akt/NF-kappaB pathway.

  • Source
    [Show abstract] [Hide abstract]
    ABSTRACT: Sprouty (Spry) proteins have previously been suggested as negative regulators of the MAPK pathway through interaction with Raf-1. However, the molecular basis of this inhibition has not been elucidated. In this study, we used cells expressing FLAGtagged Raf-1 with point mutations at known phosphorylation sites to reveal that activation of Raf-1 mutants does not correlate with their degree of interaction with Spry2. The association of Raf-1 with Spry2 in intact cells was further corroborated by immunofluorescence colocalization. Additionally, there was no significant change observed in the strength of interaction between Raf-1 mutants and Spry2 after paclitaxel treatment despite differences in the activation levels of these mutants. Thus, our study provides the evidence that Spry2 does not directly regulate Raf-1 kinase activity, but instead acts as a scaffolding protein that assists interactions between Raf-1 kinase and its direct regulators.
    BMB reports 03/2010; 43(3):205-11. DOI:10.5483/BMBRep.2010.43.3.205 · 1.99 Impact Factor

Full-text (2 Sources)

Available from
Aug 23, 2014