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Diphtheria toxin (DT) is a unique bacterial protein, which selectively kills certain cell populations due to strict functional specialization of domains that allows using this toxin in protein engineering for constructing recombinant derivatives with defined properties. The article covers structural and functional features of DT molecule, both fundamental and practical aspects of recombinant DT derivatives' applications in different fields. In particular, applications of recombinant DT derivatives as unique instruments for fundamental research of cell receptors' functions, mechanism of DT action and participation of different cell populations in biological processes are presented. Perspectives of recombinant DT derivatives practical applications for the development of vaccines, cytotoxins, HB-EGF blockers, diagnostic test-systems, serotherapeutic medications and constructions for drug delivery have been discussed. This review reflects recent advances and current problems in using recombinant DT derivatives for treatment and prophylaxis of oncologic, autoimmune, infectious and others diseases.

pivotal role in many cellular processes, but its effect differs from one cell type to another and remains not fully understood. the aim of this work was to investigate the dependence between the rate of hB-eGF mediated cell proliferation and activation of EGFR and ErbB4 receptors. Therefore, the effects of human recombinant sHB-EGF (rsHB-EGF) on the proliferation of cell lines with different EGFR and ErbB4 quantity and ratio, as well as activation of the marK-cascade p38 and erK1/2 (p42/44) kinases, were analyzed. For comparison, a similar study of the effect of native sHB-EGF secreted by human histiocytic lymphoma cells U937 during co-cultivation with different cell lines was performed. It was proved that cell proliferation in response to sHB-EGF depends not only on the quantity but also on the ratio of EGFR and ErbB4. It was shown that signaling through erbB4 is associated with activation of p38 kinase and signaling through eGFr associated with activation of ERK1/2 (p42/44) kinase. We assume the existence of two different mechanisms for sHB-eGF-mediated stimulation of cell proliferation, and the simultaneous launch of these mechanisms provides a maximal proliferative response. the results of this study support the feasibility of creating anti-proliferative drugs that target erbB4.