Changes in intracellular calpastatin localization are mediated by reversible phosphorylation.

Abstract

We have previously reported that, in neuroblastoma LAN-5 cells, calpastatin is in an aggregated state, close to the cell nucleus [de Tullio, Passalacqua, Averna, Salamino, Melloni and Pontremoli (1999) Biochem. J. 343, 467-472]. In the present paper, we demonstrate that aggregated calpastatin is predominantly in a phosphorylated state. An increase in intracellular free [Ca2+] induces both dephosphorylation of calpastatin, through the action of a phosphoprotein phosphatase, and its redistribution as a soluble inhibitor species. cAMP, but not PMA-induced phosphorylation, reverses calpastatin distribution favouring its aggregation. This intracellular reversible mechanism, regulating the level of cytosolic calpastatin, could be considered a strategy through which calpain can escape calpastatin inhibition, especially during earlier steps of its activation process.

• Authors: M Averna, R de Tullio, M Passalacqua, F Salamino, S Pontremoli, E Melloni
• Journal: The Biochemical journal (Biochem J) Vol. 354 Issue Pt 1 Pg. 25-30 (Feb 15 2001) ISSN: 0264-6021 [Print] England
• PMID: 11171075 (Publication Type: Journal Article, Research Support, Non-U.S. Gov't)

Chemical References

• Calcium-Binding Proteins
• calpastatin
• Cyclic AMP
• Cyclic AMP-Dependent Protein Kinases
• Protein Kinase C

Topics

• Calcium-Binding Proteins (metabolism)
• Chromatography, Ion Exchange
• Cyclic AMP (metabolism)
• Cyclic AMP-Dependent Protein Kinases (metabolism)
• Humans
• Phosphorylation
• Protein Kinase C (metabolism)
• Tumor Cells, Cultured