This paper reports on a potential physiological target of
okadaic acid (OA), the toxin metabolite responsible for
shellfish poisoning and, consequently, human intoxication. OA is a potent promoter of
tumor activity, most likely by inhibiting
protein phosphatase 1 and 2A (Adv.
Cancer. Res. 61 (1993) 143). However, all of its cellular targets have not yet been characterized. The interaction of OA with
alkaline phosphatase (ALP) has been investigated in view of its
protein phosphatase inhibition activity. Kinetic analysis of ALP from Escherichia coli, human placental and calf intestinal ALP has shown that OA acts as a non-competitive inhibitor of ALP. The bacterial
enzyme displays a higher affinity for OA (K(i) 360 nM) than the eukaryotic
proteins (human placental ALP, K(i) 2.05 microM; calf intestinal ALP, K(i) 3.15 microM). The inhibition by OA suggests a putative role of ALP in the phosphorylation status, through regulation of the phosphorylation/dephosphorylation equilibrium of
proteins with phosphoseryl or phosphothreonyl residues.