Group IID secretory phospholipase A2 (sPLA2-IID), a heparin-binding sPLA2 that is closely related to sPLA2-IIA, augments stimulus-induced cellular arachidonate release in a manner similar to sPLA2-IIA. Here we identified the residues of sPLA2-IID that are responsible for heparanoid binding, are and therefore essential for cellular function. Mutating four cationic residues in the C-terminal portion of sPLA2-IID resulted in abolition of its ability to associate with cell surface heparan sulfate and to enhance stimulusinduced delayed arachidonate release, cyclooxygenase-2 induction, and prostaglandin generation in 293 cell transfectants
