Wnt-11 signaling leads to down-regulation of the Wnt/beta-catenin, JNK/AP-1 and NF-kappaB pathways and promotes viability in the CHO-K1 cells.
The Wnt family of glycoprotein growth factors controls a number of central cellular processes such as proliferation, differentiation and ageing. All the Wnt proteins analyzed so far either activate or inhibit the canonical beta-catenin signaling pathway that regulates transcription of the target genes. In addition, some of them activate noncanonical signaling pathways that involve components such as the JNK, heterotrimeric G proteins, protein kinase C, and calmodulin-dependent protein kinase II, although the precise signaling mechanisms are only just beginning to be revealed. We demonstrate here that Wnt-11 signaling is sufficient to inhibit not only the canonical beta-catenin mediated Wnt signaling but also JNK/AP-1 and NF-kappaB signaling in the CHO cells, thus serving as a noncanonical Wnt ligand in this system. Inhibition of the JNK/AP-1 pathway is mediated in part by the MAPK kinase MKK4 and Akt. Moreover, protein kinase C is involved in the regulation of JNK/AP-1 by Wnt-11, but not of the NF-kappaB pathway. Consistent with the central role of Akt, JNK and NF-kappaB in cell survival and stress responses, Wnt-11 signaling promotes cell viability. Hence Wnt-11 is involved in coordination of key signaling pathways.
Oulu Centre for Cell-Matrix Research, Biocenter Oulu and Department of Medical Biochemistry and Molecular Biology, University of Oulu, P.O.B. 5000, 90014 University of Oulu, Finland.
Antti
A
Railo
Irina I
II
Nagy
Pekka
P
Kilpeläinen
Seppo
S
Vainio
D000818:Animals; D017209:Apoptosis / Q000187:drug effects / Q000502:physiology; D016466:CHO Cells; D002470:Cell Survival; D006224:Cricetinae; D003412:Cricetulus; D015536:Down-Regulation / Q000235:genetics; D048031:JNK Mitogen-Activated Protein Kinases / Q000378:metabolism*; D020929:Mitogen-Activated Protein Kinase Kinases / Q000378:metabolism / Q000502:physiology; D016328:NF-kappa B / Q000378:metabolism*; D051058:Oncogene Protein v-akt / Q000502:physiology; D015398:Signal Transduction / Q000187:drug effects / Q000502:physiology; D018808:Transcription Factor AP-1 / Q000378:metabolism*; D014162:Transfection; D051153:Wnt Proteins / Q000235:genetics / Q000378:metabolism / Q000502:physiology*; D051176:beta Catenin / Q000378:metabolism*
D016328:NF-kappa B; D018808:Transcription Factor AP-1; D051153:Wnt Proteins; D051176:beta Catenin; D051058:Oncogene Protein v-akt; D048031:JNK Mitogen-Activated Protein Kinases; D020929:Mitogen-Activated Protein Kinase Kinases