Phosphorylation signalling pathways

The abundance of many protein kinases in cells is an indication of the great importance of protein phosphorylation in cellular regulation. Exactly 113 protein kinase genes have been recognized in yeast, and it is estimated that the human genome encodes more than 1000 different protein kinases. Tyrosine kinases (protein kinases that phosphorylate Tyr residues) occur only in multicellular organisms (yeast has no tyrosine kinases). Tyrosine kinases are components of signaling pathways involved in cell-cell communication (see Chapter 34). 

PRs also interact with other signaling pathways, which can, e.g., be regulated by phosphorylation. Independent of transcriptional activation of PR, progestins can activate cytoplasmic signaling molecules including SRC and downstream MAP kinase in mammalian cells via interaction by a specific polyproline motif in the N-terminal domain of PR. 

The third signalling pathway of TRIF utilises its C-terminus. This region contains a RJQP homology interaction motif (RHIM) that binds RJQP-1 and REP-3. RIP-1 phosphorylates IKK-(3 and the NFkB pathway can be activated. REP-3 is a negative regulator of TREF competing for REP-1 [2]. 

The inhibition of the phosphorylation of IkBoc by celastrol in the NF-kB signaling pathway is not cell specific72-75 and thus significantly broadened the potential medicinal applications of natural triterpene QMs. Celastrol 76 has been evaluated in the treatment of Crohn s disease,76 which is a chronic relapsing inflammatory bowel disease. In the peripheral blood mononuclear cells, celastrol 76 reduced the levels of... 

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