THE BIOLOGY OF SPARC, A PROTEIN THAT MODULATES CELL-MATRIX INTERACTIONS

An extracellular matrix-associated glycoprotein expressed in a variety of tissues during embryogenesis and repair, SPARC contains modular do mains that can function independently to bind cells and matrix compone nts. Because SPARC can selectively disrupt cellular contacts with matr ix and thereby effect changes in cell shape, it has been referred to a s an antiadhesin. Inhibition of the expression of SPARC altered axial development in frogs, and deregulated expression in nematode worms res ulted in a derangement of muscle attachment and embryonic lethality. S PARC also inhibits cell cycle progression in vitro, in part through a cationic, disulfide-bonded region that is homologous to a repeated dom ain in the cytokine inhibitor, follistatin. Moreover, SPARC binds spec ifically to the B chain of platelet-derived growth factor and alters t he response of cells to several cytokines. Although information concer ning the expression, biochemical properties, and cellular activities o f SPARC has increased significantly over the last decade, the precise function of the protein has not been resolved. Goals of future studies include characterization of cell-surface receptors for SPARC and the interactions with morphogens and growth factors that regulate specific activities during animal development.