Dimerization choices control the ability of axin and dishevelled to activate c-jun N-terminal kinase/stress-activated protein kinase

Axin and Dishevelled are two downstream components of the Wnt signaling pat hway. Dishevelled is a positive regulator and is placed genetically between Frizzled and glycogen synthase kinase-3 beta, whereas Axin is a negative r egulator that acts downstream of glycogen synthase kinase-3 beta. It is int riguing that they each can activate the c-Jun N-terminal kinase/stress-acti vated protein kinase (JNK/SAPK) when expressed in the cell. We set out to a ddress if Axin and Dishevelled are functionally cooperative, antagonistic, or entirely independent, in terms of the JNK activation event. We found tha t in contrast to Axin, Dv12 activation of JNK does not require MEKK1, and c omplex formation between Dv12 and Axin is independent of Axin-MEKK1 binding . Furthermore, Dv12-DIX and Dv12-Delta DEP proteins deficient for JNK activ ation can attenuate Axin-activated JNK activity by disrupting Axin dimeriza tion. However, Axin-Delta MID, and Axin-Delta T proteins deficient for JNK activation cannot interfere with Dv12-activated JMK activity. These results indicate that unlike the strict requirement of homodimerization for Axin f unction, Dv12 can activate JNK either as a monomer or homodimer/heterodimer . We suggest that there may be a switch mechanism based on dimerization com binations, that commands cells to activate Wnt signaling or JNK activation, and to turn on specific activators of JNK in response to various environme ntal cues.