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Another overlooked feature of the hemeHPX cell interaction is the activation of signaling cascades, including the N-terminal cJun-kinase (JNK) pathway ( Furthermore, with respect to apo-HPX recycling in the context of HPX binding to a surface receptor, we consider that heparin binding to apo-HPX, but not hemeHPX, models an interaction between hemeHPX with an HPX receptor-associated surface HSPG, as suggested for holo-Tf and TfR1 (Regoeczi et al., 1994)