SELECTIVE ACTIVATION OF THE JNK SIGNALING CASCADE AND C-JUN TRANSCRIPTIONAL ACTIVITY BY THE SMALL GTPASES RAC AND CDC42HS

The Rho subfamily of GTPases is involved in control of cell morphology In mammals and yeast. The mammalian Rac and Cdc42 proteins control fo rmation of lamellipodia and filopodia, respectively. These proteins al so activate MAP kinase (MAPK) cascades that regulate gene expression. Constitutively activated forms of Rac and Cdc42Hs are efficient activa tors of a cascade leading to JNK and p38/Mpk2 activation. RhoA did not exhibit this activity, and none of the proteins activated the ERK sub group of MAPKs. JNK, but not ERK, activation was also observed in resp onse to Dbl, an oncoprotein that acts as a nucleotide exchange factor for Cdc42Hs. Results with dominant interfering alleles place Rac1 as a n intermediate between Ha-Ras and MEKK in the signaling cascade leadin g from growth factor receptors and v-Src to JNK activation. JNK and p3 8 activation are likely to contribute to the biological effects of Rac , Cdc42Hs, and Dbl on cell growth and proliferation.