Protein kinase C-dependent phosphorylation regulates osteoclast calcium-sensing
Argentino, L.; Colucci, S.; Grano, M.; Barattolo, R.; Zambonin Zallone, A.; Teti, A.
Bollettino della Societa Italiana di Biologia Sperimentale 68(4): 245-248
1992
ISSN/ISBN: 0037-8771 PMID: 1463597 Document Number: 399585
Osteoclasts display a membrane Ca-2+-sensing mechanism capable of detecting the extracellular calcium concentration ((Ca-2+)-o), and to induce increase of (Ca-2+)-i and inhibition of bone resorption. The ultimate result of the stimulation of such sensing is probably the activation of protein kinase C (PKC). To demonstrate whether PKC plays a role in the control of the osteoclast activity, we treated rabbit single osteoclasts with agents known to activate or to inhibit the enzyme. We measured (Ca-2+)-i in single fura 2-loaded single cells and found that activation of PKC by phorbol esters doubled the (Ca-2+)-o-induced (Ca-2+)-i elevation, whereas inhibition of the enzyme by H7, staurosporin or sphingosine, completely blocked the ability of the cell to respond to elevated (Ca-2+)-i. By contrast, a control inactive agent, 4A-phorbol, failed to modify the cellular response to elevated (Ca-2+)-o. We conclude that PKC plays a synergistic role in the regulation of osteoclast Ca-2+-sensing. Since we have previously demonstrated that activation of PKA up-regulates the Ca-2+-sensing as well, we hypothesize that such mechanism is positively fed-back by both PKA and PKC-dependent threonine/serine phosphorilations.