Control of osteopontin signaling and function by post-translational phosphorylation and protein folding


  • The authors dedicate this article to the memory of Dr. Jaro Sodek, a true gentleman/scholar and one of the pioneers of OPN and BSP research. Among his many seminal contributions are the discovery of intracellular OPN and the complex role OPN plays in inflammatory processes. A life cut short in its prime, he will be sorely missed; never again will DTD share a few beers with him at the Black Dog Pub.


Osteopontin (OPN) plays roles in a variety of cellular processes from bone resorption and extracellular matrix (ECM) remodeling to immune cell activation and inhibition of apoptosis. Because it binds receptors (integrins, CD44 variants) typically engaged by ECM molecules, OPN acts as a “soluble” ECM molecule. A persistent theme throughout the characterization of how OPN functions has been the importance of phosphorylation. The source of the OPN used in specific experiments and the location of modified sites is an increasingly important consideration for OPN research. We review briefly some of the ways OPN impacts on the biology of mammalian systems with an emphasis on the importance of serine phosphorylation in modulating its signaling ability. We describe experiments that support the hypothesis that differences in the post-translational phosphorylation of OPN expressed by different cell types regulate how it impacts on target cells. Analyses of OPN's potential secondary structure reveal a possible beta-sheet conformation that offers an interpretation of certain experimental observations, specifically the effect of thrombin cleavage; it is consistent with an interaction between the C-terminal region of the protein and the central integrin-binding RGD sequence. J. Cell. Biochem. 102: 912–924, 2007. © 2007 Wiley-Liss, Inc.