Premium
Signal transduction pathways are altered by cellular labile iron
Author(s) -
Hegde Narasimha,
Hao Lei,
Unger Erica,
Han Okhee,
Beard John
Publication year - 2009
Publication title -
the faseb journal
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.709
H-Index - 277
eISSN - 1530-6860
pISSN - 0892-6638
DOI - 10.1096/fasebj.23.1_supplement.921.9
Subject(s) - internalization , protein kinase c , signal transduction , microbiology and biotechnology , cytosol , gene isoform , endocytic cycle , phosphorylation , chemistry , population , confocal microscopy , biology , cell , biochemistry , gene , endocytosis , enzyme , demography , sociology
The cellular labile iron pool (LIP), which represents <5% of the total cellular iron is associated with a diverse population of ligands such as organic anions, polypeptides, and surface components of membranes. LIP as a self‐regulatory pool that is sensed by cytosolic iron regulatory proteins (IRPs) and feedback regulated by IRP‐dependent expression of iron import and storage proteins. Variation in the LIP can also contribute to basic cellular signaling events. In these studies we examined the effect of LIP variation on cell surface processes mediated by protein kinase C (PKC) in a model system of neuroblastoma cells. Levels of isoforms of PKC were highly sensitive to LIP while PKC beta isoform being more susceptible to change. Confocal microscopy studies suggest increased ubiqitination and internalization of membrane proteins and are consistent with qRT‐PCR gene array analysis of signaling pathways. Lower LIP levels result in increased ubiqitination, increased phosphorylation, and lower rates of endocytic protein recycling. The proximal "switch" for this activation is being explored. This ongoing study is supported by USDA (# 2007‐35200‐18231).