In addition to its activation, ALOX5 must gain access to its polyunsaturated fatty acid (PUFA) substrates, which commonly are bound in an ester linkage to the "sn"2 position of membrane phospholipids (see phospholipid), in order to form biologically active products. This is accomplished by a large family of phospholipase A2 (PLA2) enzymes. The cytosolic PLA2 set (i.e. cPLA2s) of PLA2 enzymes (cPLA2; see Phospholipase A2#Cytosolic phospholipases A2) in particular mediates many instances of stimulus-induced release of PUFA in inflammatory cells. For example, chemotactic factors stimulate human neutrophils to raise cytosolic Ca2+ which triggers cPLA2s, particularly the α isoform (cPLA2α), to move from its normal residence in the cytosol to cellular membranes. This chemotactic factor stimulation concurrently causes the activation of mitogen-activated protein kinases (MAPK) which in turn stimulates the activity of cPLA2α by phosphorylating it on ser-505 (other cell types may activate this or other cPLA2 isoforms using other kinases which phosphorylate them on different serine residues). These two events allow cPLA2s to release PUFA esterified to membrane phospholipids to FLAP which then presents them to ALOX5 for their metabolism.