RAC MEDIATES GROWTH FACTOR-INDUCED ARACHIDONIC-ACID RELEASE

Growth factor-induced stress fiber formation involves signal transduct ion through Rac and Rho proteins and production of leukotrienes from a rachidonic acid metabolism. In exploring the relationship between thes e pathways, we found that Rac is essential for EGF-induced arachidonic acid production and subsequent generation of leukotrienes and that Ra c V12, a constitutively activated mutant of Rac, generates leukotriene s in a growth factor-independent manner. Leukotrienes generated by EGF or Rac V12 are necessary and sufficient for stress fiber formation. F urthermore, leukotriene-dependent stress fiber formation requires Rho proteins. We have therefore identified elements of a pathway from grow th factor receptors that includes Rac, arachidonic acid production, ar achidonic acid metabolism to leukotrienes, and leukotriene-dependent R ho activation. This appears to be the major pathway by which Rac influ ences Rho-dependent cytoskeleton rearrangements.