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|Title:||Axin forms a complex with MEKK1 and activates c-Jun NH2-terminal kinase/stress-activated protein kinase through domains distinct from Wnt signaling||Authors:||Zhang, Y.
|Issue Date:||3-Dec-1999||Citation:||Zhang, Y., Neo, S.Y., Wang, X., Han, J., Lin, S.-C. (1999-12-03). Axin forms a complex with MEKK1 and activates c-Jun NH2-terminal kinase/stress-activated protein kinase through domains distinct from Wnt signaling. Journal of Biological Chemistry 274 (49) : 35247-35254. ScholarBank@NUS Repository. https://doi.org/10.1074/jbc.274.49.35247||Abstract:||Axin negatively regulates the Wnt pathway during axis formation and plays a central role in cell growth control and tumorigenesis. We found that Axin also serves as a scaffold protein for mitogen-activated protein kinase activation and further determined the structural requirement for this activation. Overexpression of Axin in 293T cells leads to differential activation of mitogen-activated protein kinases, with robust induction for c- Jun NH2-terminal kinase (JNK)/stress-activated protein kinase, moderate induction for p38, and negligible induction for extracellular signal- regulated kinase. Axin forms a complex with MEKK1 through a novel domain that we term MEKK1-interacting domain. MKK4 and MKK7, which act downstream of MEKK1, are also involved in Axin-mediated JNK activation. Domains essential in Wnt signaling, i.e. binding sites for adenomatous polyposis coli, glycogen synthase kinase-3β, and β-catenin, are not required for JNK activation, suggesting distinct domain utilization between the Wnt pathway and JNK signal transduction. Dimerization/oligomerization of Axin through its C terminus is required for JNK activation, although MEKK1 is capable of binding C terminus- deleted monomeric Axin. Furthermore, Axin without the MEKK1-interacting domain has a dominant-negative effect on JNK activation by wild-type Axin. Our results suggest that Axin, in addition to its function in the Wnt pathway, may play a dual role in cells through its activation of JNK/stress- activated protein kinase signaling cascade.||Source Title:||Journal of Biological Chemistry||URI:||http://scholarbank.nus.edu.sg/handle/10635/111795||ISSN:||00219258||DOI:||10.1074/jbc.274.49.35247|
|Appears in Collections:||Staff Publications|
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