Angiotensin II induces phosphorylation of glucose-regulated protein-75 in WB rat liver cells

• Published in: Archives of biochemistry and biophysics 2007-01, Vol.457 (1), p.16-28
• Main Authors: Krishna, Sharath B., Alfonso, Lloyd F., Thekkumkara, Thomas J., Abbruscato, Thomas J., Jayarama Bhat, G.
• Format: Article
• Language: English
• Subjects: Amino Acid Sequence; Amino Acids - metabolism; Angiotensin II; Angiotensin II - pharmacology; Angiotensin II - physiology; Animals; Caveolin 1 - metabolism; Cell Line; Chaperone; Cytoplasm - metabolism; EGF-R transactivation; Enzyme Activation; Extracellular Signal-Regulated MAP Kinases - metabolism; GRP-75; HSP70 Heat-Shock Proteins - metabolism; Liver - cytology; Membrane Proteins - metabolism; Mitochondria; Mitochondria, Liver - metabolism; Molecular Sequence Data; Oxidative Stress; Phosphorylation; Rats; Receptor, Epidermal Growth Factor - metabolism; Signal Transduction; STAT3 Transcription Factor - metabolism; Transcriptional Activation
• ISSN: 0003-9861; 1096-0384
• DOI: 10.1016/j.abb.2006.10.011

Studies in vascular smooth muscle cells suggest that, angiotensin II (Ang II)-mediated cellular response requires transactivation of epidermal growth factor receptor (EGF-R), and involves tyrosine phosphorylation of caveolin-1. Here we demonstrate that, exposure of WB rat liver cells to Ang II does not cause transactivation of EGF-R, but did rapidly activate p42/p44 mitogen-activated protein (MAP) kinases suggesting that it activates MAP kinases independent of EGF-R transactivation. We observed that the phospho-specific anti-caveolin-1 antibody detected a tyrosine phosphorylated, 75 kDa protein in Ang II-treated cells which we identified as glucose regulated protein-75 (GRP-75). Phosphoamino acid analysis showed that Ang II induced its phosphorylation at tyrosine, serine and threonine residues and was localized to the cytoplasm. The ability of Ang-II to induce GRP-75 phosphorylation suggests that it may play a role in the protection of cytoplasmic proteins from the damaging effect of oxidative stress known to be produced during Ang-II induced signaling.