Points of convergence between Ca 2+ and Ras signalling pathways

Abstract

p21 Ras proteins play a critical role in the regulation of cellular growth and differentiation. In addition, Ras and proteins which regulate Ras activity have been implicated in long-term memory consolidation and long-term potentiation processes. Over the last few years, much evidence has emerged which indicates that changes in cytoplasmic Ca 2+ levels can regulate Ras protein activity and subsequent biological function. Also, Ras proteins themselves can modulate intracellular Ca 2+ levels by regulating both Ca 2+ release and Ca 2+ influx processes. Here we examine the signalling components which regulate Ras activity and, in particular, consider points of convergence between intracellular Ca 2+ and p21 Ras signalling processes. In addition, we consider the possible biological consequences resulting from the integration of these signalling pathways and highlight the importance of our understanding protein–protein interactions. Finally, we discuss the possibility of protein–protein interactions mediated via Ca 2+-responsive structural domains, such as the C2 and IQ domains, playing important roles in Ca 2+-dependent Ras functions yet to be established.