RAC MEDIATES GROWTH FACTOR-INDUCED ARACHIDONIC-ACID RELEASE

Growth factor-induced stress fiber formation involves signal transduction through Rac and Rho proteins and production of leukotrienes from arachidonic acid metabolism. In exploring the relationship between these pathways, we found that Rac is essential for EGF-induced arachidonic acid production and subsequent generation of leukotrienes and that Rac V12, a constitutively activated mutant of Rac, generates leukotrienes in a growth factor-independent manner. Leukotrienes generated by EGF or Rac V12 are necessary and sufficient for stress fiber formation. Furthermore, leukotriene-dependent stress fiber formation requires Rho proteins. We have therefore identified elements of a pathway from growth factor receptors that includes Rac, arachidonic acid production, arachidonic acid metabolism to leukotrienes, and leukotriene-dependent Rho activation. This appears to be the major pathway by which Rac influences Rho-dependent cytoskeleton rearrangements.