Distending Toxin Cdt

Cdt is related to a eukaryotic cytosolic enzyme, phosphatidyl inositol-3,4,5, triphosphate 5-phosphatase which removes the 5-phosphate group from phosphatidyl inositol-3,4,5, triphosphate. This activity is part of an intracellular signaling cascade induced by a ligand binding to a nearby receptor. Phosphatidyl inositol-3,4,5-triphosphate 5-phosphatase possesses an Src Homology 2 (SH2) domain in addition to its Inositol Phosphatase activity (SHIP). 

The SH2 domain is a conserved sequence in a viral tyrosine kinase responsible for transforming fibroblasts into neoplastic sarcoma cells (the viral src gene, v-src, see sect. 10.2.1. for the normal cell counterpart, c-src). SHI is a tyrosine kinase domain SH2 is the domain that binds to phosphotyrosine residues and SH3 is a v-src domain that binds to proline-rich sequences in proteins. SH2 and SH3 domains are found in many proteins involved in signal transduction. 

Cdt is composed of three proteins, all encoded by the cdt operon. Two of these proteins bind to human cell membranes where they facilitate the translocation of the third subunit, a SHEP-like phosphatase PI-3,4,5-triphosphate 5-phosphatase. This bacterial phosphatase passes through the membrane and removes the 5-phosphate from PI-3,4,5-triphosphate, causing stimulated lymphocytes and macrophages to undergo apoptosis instead of growth. In nonleukocytic cells such as epidermal cells or fibroblasts, PI-3,4,5-phosphatase is exposed to PTEN, which is 10 times more active on PI-3,4,5-triphosphate than Cdt. The S I I IP-1 ike bacterial enzyme therefore cannot compete with PTEN. The sensitivity of nonleukocytic cells to Cdt is much less than that of stimulated lymphocytes and macrophages. 

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