MOLECULAR-BASIS OF GROWTH-REGULATION BY C ELL CONTACT

The growth of mammalian cells is under the stringent control of both g rowth stimulatory and inhibitory signals. While a series of growth sti mulatory compounds, their receptors and the intracellular signals gene rated by their interaction have been studied in detail, little is know n about growth inhibitory compounds. A major growth negative regulatio n, especially in vitro, is exerted by specific cell-cell contacts, kno wn as contact dependent inhibition of growth. Here, a recently isolate d plasma membrane glycoprotein referred to as contactinhibin induces g eneration of intracellular growth inhibiting signals by binding to a s pecific receptor. The binding activity of the receptor is inversely re gulated by its degree of phosphorylation. In transformed cells, the re ceptor is overphosphorylated thereby impairing its contactinhibin bind ing activity, resulting in loss of growth inhibition. Overphosphorylat ion may result from activation of oncogene encoded protein kinases, su ggesting that contactinhibin-receptor may be a crucial and central sub strate for growth-dysregulating processes in transformed cells.