Calcium signals in growth factor signal transduction.

There is a substantial amount of information which has been obtained concerning the effects of growth factors on [Ca2+]i in proliferating cells. A number of different mitogens are known to induce elevations in [Ca2+]i and some characterization of the Ca2+ response to different classes of mitogens has been obtained. In addition, much is known about whether the Ca2+ response to a particular growth factor occurs as the result of an influx of external Ca2+ or a mobilization of internal Ca2+ stores. In addition, a considerable amount of information is available on the mechanism by which the Ins(1,4,5)P3-sensitive internal Ca2+ store takes up and releases Ca2+. However, there is still a large deficiency in our information concerning other Ca2+ stores in proliferating cells as well as in our knowledge of the mechanisms for regulating Ca2+ entry pathways. Much more data addressing these issues exists for other types of agonist-stimulated cells, and we have discussed much of it in this review article. While the wealth of data in nonproliferating cells provides some indications of what mechanisms might be involved in the growth factor-induced changes in [Ca2+]i, it is clear that much work must be done in proliferating cells to fully understand how external factors such as growth factors control [Ca2+]i. In addition, much work remains to be done in identifying the mechanisms for the internal control of [Ca2+]i as cells move through the cell cycle and in identifying the role that these changes in [Ca2+]i may play throughout the cell cycle.