Complexes to coordinate calcium

On page 657, Hur et al. show that signaling complexes on the plasma membrane and ER, and two different signals, unite to coordinate calcium release.Many signaling pathways, sometimes in specific combinations, lead to calcium release from internal ER stores. In adrenal chromaffin cells, EGF alone does not cause store release unless the cells are first stimulated with bradykinin (BK), which is an inflammation-generated hormone.

Hur and colleagues show that this sensitized release requires BK's known ability to activate PKA. PKA was found in a large complex that linked the plasma membrane and the ER. The complex also included the EGF receptor (on the plasma membrane), the calcium-release channel IP₃R1 (which was found in the ER), and a tethering protein called AKAP9.

The binding of EGF to its receptor generates...