Phospholipid-mediated signaling involves the production of messengers through phospholipases and/or lipid kinases. One example involves the PIP2 pathway. PIP 2 are substrates for enzymes such as PLC. PLC is a protein which regulates the levels of PIP in cells through the localization of lipids in the membrane and catalyzing the hydrolysis of phosphatidylinositol following stimuli. When receptors are activated, PLC cleaves PIP2 to make inositol triphosphate (IP3) and diacylglycerol (DAG), which remains bound to the membrane. DAG activates protein kinase C, which then phosphorylates molecules such as AKT to activate processes including cell proliferation, spatial distribution of cells, and cell polarity. IP3 releases calcium ions from intracellular stores within the ER. The cytoplasmic calcium levels are subsequently increased and induce a calcium spike which triggers cell activation. Molecules derived from phospholipids also have significant roles in modulating exocytosis, endocytosis and the exo/endocytosis balance. In exocytosis, phospholipids are vital for forming vesicles which assist in breaking down cell material. Phospholipids also modulate endocytosis processes which are vital for growth, cell migration, and synaptic transmission. The phospholipid lysobisphosphatidic acid also has a role in the regulation of the membrane invagination during endocytosis, as well as endosome biogenesis. During periods of biological stress, the communication between phospholipid-based signaling and the movement of membranes assists in signal recognition and triggering immune responses.