Protein kinase inhibitors signal transduction

K252a family of alkaloid toxins isolated from microbes represent the second generation of natural protein-kinase inhibitors (Rasouly et al., 1995). During the last decade they have been intensively used in studies aimed at elucidating the cellular role of protein kinases in signal transduction pathways and different biological functions (Parker et al., 1992). 

Burke, T. R. Jr., Yao, Z.-J., Smyth, M. S., and Ye, B. (1997) Phosphotyrosyl-based motifs in the structure-based design of protein-tyrosine kinase-dependent signal transduction inhibitors. Curr. Pharm. Des. 3, 291-304. 

Signal-transduction pathways and cancer (p. 400) Monoclonal antibodies as anlicancer drugs (p. 401) Protein kinase inhibitors as anticancer drugs (p. 401) Cholera and whooping cough (p. 401)... 

Mikalsen T, Gerits N, Moens U (2006) Inhibitors of signal transduction protein kinases as targets for cancer therapy. Biotechnol Annu Rev 16 153-223... 

In contrast to inhibitor 1, DARPP-32 and NIPP1, which regulate signal transduction, the function of inhibitor 2 appears to be different. There is evidence that inhibitor 2 associates with PP1, as the phosphatase is newly synthesized and contributes to the proper folding of the enzyme [40]. Inhibitor 2 can thus be considered a chaperone protein. The inactive PP 1-inhibitor 2 complex can then be activated upon phosphorylation of inhibitor 2 by glycogen synthase kinase-3. Whether this process is regulated in neurons in association with synaptic activity remains unknown. 

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