Enzymes in mineralizing systems: state of the art.

The hallmark of biological mineralization is the precise regulation of mineral deposition in space and time. The cells which produce mineralized tissues are themselves controlled by developmental programs and hormonal signals which result in regulation of gene expression and modulation of protein function. These signals are transduced into changes in enzyme levels and/or activity. Upon activation, cellular enzymes then act to synthesize the organic matrix and process it extracellularly, utilize metabolic energy to transport ions from the blood to the matrix, and to initiate the mineralization cascade. The first enzyme activity described in mineralizing tissues was alkaline phosphatase and it is still the best characterized enzyme in the mineralization process. Yet, important questions about the role of this protein remain unanswered, and it continues to occupy a central focus in mineralized tissue investigation. Other phosphatases, including protein tyrosine phosphatases are important in regulating tyrosine kinase mediated signals. Investigators have now begun to look closely at several groups of kinases which are also important for proper mineralization. As peptide hormones are important modulators of mineralized tissues, protein kinase A has always been presumed to play a key role in phosphorylating intracellular proteins. There is also considerable interest in protein kinase C, as well as tyrosine kinases in mineralized tissue signal transduction. Another group of kinases important in mineralized tissues are the enzymes which phosphorylate the matrix phosphoproteins. Of these, casein kinase II appears to be involved in intracellular and extracellular protein phosphorylation. Several enzymes present in the premineralized matrix are thought to be significant in triggering mineralization. Alkaline phosphatase may act at this level, but new data also suggests that metalloproteases and gelatinases, by modifying or digesting matrix components, may be important in the initiation of calcification.