In this chapter, we have focused on individual signaling pathways to illustrate the general principles of communication between cells. In each case, we saw that a cell releases a signaling molecule or in some cases retains the signaling molecule attached to its surface. The signaling molecule binds to a cell-surface or intracellular receptor. Binding of the signaling molecule induces a conformational change in the receptor, causing it to become active. The activated receptor in turn causes changes in the interior of the cell, frequently turning on a signal transduction cascade that is amplified and leads to a cellular response. Eventually, the response terminates, and the cell is poised to receive new signals.

Focusing on each pathway one at a time allowed us to understand how each pathway operates. But in the context of an entire organism or even a single cell, cell signaling can be quite complex, with multiple pathways acting at once and interacting with one another.

Multiple types of signaling molecules can bind to a single cell and activate several signaling pathways simultaneously. In this case, a cell’s final response depends on how the pathways intersect with one another. The integration of different signals gives cells a wide range of possible responses to their environment. Receiving two different signals may enhance a particular response, such as cell growth, or one signal may inhibit the signaling pathway triggered by the other signal, weakening the response.

For example, studies have shown that enzymes in the MAP kinase pathway can be inhibited by active PKA. Recall that PKA is activated by elevated cAMP levels associated with the G protein-coupled receptor pathway. The regulation of the MAP kinase pathway by PKA illustrates how one signaling pathway can inhibit another.

Researchers have started to make use of this molecular crosstalk. Many patients with breast cancer have elevated MAP kinase activity in their tumor cells. When human breast cancer cells are genetically modified to express an activated G protein α subunit, their growth after transplantation into mice is significantly inhibited. In addition, in cell culture, elevated cAMP levels block cells from responding to growth factors that signal through Ras to the MAP kinase pathway. As we better understand how different signaling pathways integrate in specific cell types, we have a chance to alter the activity of particular pathways and ultimately the response of the cell.