Protein tyrosine kinases intracellular second messengers

There are several mechanisms whereby antidepressants can modify intracellular events that occur proximal to the posts)maptic receptor sites. Most attention has been paid to the actions of antidepressants on those pathways that are controlled by receptor-coupled second messengers (such as cyclic AMP, inositol triphosphate, nitric oxide and calcium binding). However, it is also possible that chronic antidepressant treatment may affect those pathways that involve receptor interactions with protein tyrosine kinases, by increasing specific growth factor synthesis or by regulating the activity of proinflammatory cytokines. These pathways are particularly important because they control many aspects of neuronal function that ultimately underlie the ability of the brain to adapt and respond to pharmacological and environmental stimuli. One mechanism whereby antidepressants could increase the s)mthesis of trophic factors is... 

Growth hormones, important in diabetes and cancer, activate a receptor with an intrinsic intracellular tyrosine protein kinase activity that passes on the signal by phosphorylating other proteins, often kinases themselves. To date, no specific second messengers have been associated with these systems. The amplification occurs by the turn-on of the receptor-associated protein kinase activity that can phosphorylate many proteins. 

PLCy is a member of PLC family proteins (other members are PLC(5, PLC5, PLCs, PLCi etc.) that hydrolyzes phosphatidylinositol 4,5-bisphosphate into DG and IP3, both of which are second messenger to promote PKC activation and intracellular Ca mobilization, respectively (Rhee 2001). PLCy is the first example of non-tyrosine kinase protein, whose structure contains SH2 and SH3 domains (Stahl et al. 1988). PLCy is also unique in its regulatory mechanism, where tyrosine phosphorylation of the protein can up-regulate the enzyme activity. Under this background, fxmction of PLCy in oocyte maturation and fertilization has been analyzed extensively in relation to tyrosine kinase signaling. In fact, tyrosine kinase-dependent activation of PLCy at fertilization has been demonstrated in some... 

---