The
versatility of Ca<sup>2+</sup> signals allows it to regulate diverse
cellular processes such as migration, apoptosis, motility and exocytosis.
In some receptors (<i>e.g.</i>, VEGFR2), Ca<sup>2+</sup> signals are generated upon binding their ligand(s) (<i>e.g.</i>, VEGF-A). Here, we employed a design strategy to engineer proteins
that generate a Ca<sup>2+</sup> signal upon binding various extracellular
stimuli by creating fusions of protein domains that oligomerize to
the transmembrane domain and the cytoplasmic tail of the VEGFR2. To
test the strategy, we created chimeric proteins that generate Ca<sup>2+</sup> signals upon stimulation with various extracellular stimuli
(<i>e.g.</i>, rapamycin, EDTA or extracellular free Ca<sup>2+</sup>). By coupling these chimeric proteins that generate Ca<sup>2+</sup> signals with proteins that respond to Ca<sup>2+</sup> signals,
we rewired, for example, dynamic cellular blebbing to increases in
extracellular free Ca<sup>2+</sup>. Thus, using this design strategy,
it is possible to engineer proteins to generate a Ca<sup>2+</sup> signal
to rewire a wide range of extracellular stimuli to a wide range of
Ca<sup>2+</sup>-activated processes