Second Messenger Interactions on Arachidonate Mobilization

The arachidonic acid cascade takes part in a large number of functional interactions with other intracellular second messenger systems. As one would expect from their universal regulatory functions in the physiology of mammalian cells, protein phosphorylation and dephosphorylation play a major part in modulating arachidonate mobilization. Two multifunctional (and ubiquitous) protein kinases, PKC and PKA, have been studied extensively in this regard. 

Activation of PKC causes in most cells an increased stimulus-dependent mobilization of arachidonate. As we have seen, the mechanism of this enhancement is not entirely understood, but it likely involves a cascade of biochemical events leading to the phosphorylation and activation of cytosolic group IV PLA2. The possible significance of this modulatory effect—a priming of cells in view of an increased response to upcoming stimuli—has been pointed out, yet some of its offshoots may also prove to be of some interest. 

Unlike PKC, the effects of PKA activity on arachidonate mobilization can be either stimulatory or inhibitory, and they largely depend on the cell type and on the nature of the stimulus. Moreover, the available data make it difficult to draw any conclusion as to the biochemical mechanism of these effects, except perhaps that they are not likely to entail the direct phosphorylation of a PLA2- 

Kolesnick R, Golde DW. The sphingomyelin pathway in tumor necrosis factor and interleukin signaling. Cell 1994 77 325-328. 

Wakil SJ, Barnes EM. Fatty acid metabolism. Comprehensive Biochem 1971 185 57-104. 

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