Inositol 1,4,5-trisphosphate 3-kinase (IP3-3K) catalyses the phosphorylation of inositol 1,4,5-trisphosphate to inositol 1,3,4,5-tetrakisphosphate. cDNAs encoding three mammalian isoforms have been reported and referred to as IP3-3KA, IP3-3KB, and IP3-3KC. IP3-3KB is particularly sensitive to proteolysis at the N-terminus, a mechanism known to generate active fragments of lower molecular mass. Endogenous IP3-3KB has therefore not been formally identified in tissues. We have probed a series of murine tissues with an antibody directed against the C-terminus of IP3-3KB and used IP3-3KB deficient mouse tissues as negative controls. IP3-3KB was shown to be particularly well expressed in brain, lung, and thymus with molecular masses of 110-120 kDa. The identification of the native IP3-3KB by Western blotting for the first time will facilitate further studies of regulation of its activity by specific proteases and/or phosphorylation. (C) 2004 Elsevier Inc. All rights reserved.