PKC delta is essential for Dishevelled function in a noncanonical Wnt pathway that regulates Xenopus convergent extension movements.
Protein kinase C (PKC) has been implicated in the Wnt signaling pathway; however, its molecular role is poorly understood. We identified novel genes encoding delta-type PKC in the Xenopus EST databases. Loss of PKC delta function revealed that it was essential for convergent extension during gastrulation. We then examined the relationship between PKC delta and the Wnt pathway. PKC delta was translocated to the plasma membrane in response to Frizzled signaling. In addition, loss of PKC delta function inhibited the translocation of Dishevelled and the activation of c-Jun N-terminal kinase (JNK) by Frizzled. Furthermore, PKC delta formed a complex with Dishevelled, and the activation of PKC delta by phorbol ester was sufficient for Dishevelled translocation and JNK activation. Thus, PKC delta plays an essential role in the Wnt/JNK pathway by regulating the localization and activity of Dishevelled.
Kinoshita
Noriyuki
N
Department of Developmental Biology, National Institute for Basic Biology, Myodaiji, Okazaki, Aichi 444-8585, Japan. nkinoshita@nibb.ac.jp
Iioka
Hidekazu
H
Miyakoshi
Akira
A
Ueno
Naoto
N
D028341:Activins / Q000494:pharmacology; D048868:Adaptor Proteins, Signal Transducing; D000595:Amino Acid Sequence; D000818:Animals; D020134:Catalytic Domain; D002454:Cell Differentiation; D002462:Cell Membrane / Q000201:enzymology; D000072261:Dishevelled Proteins; D004625:Embryo, Nonmammalian / Q000201:enzymology / Q000502:physiology*; D004789:Enzyme Activation; D005775:Gastrula / Q000502:physiology*; D048031:JNK Mitogen-Activated Protein Kinases; D048688:MAP Kinase Kinase 7; D008648:Mesoderm / Q000166:cytology / Q000502:physiology; D020929:Mitogen-Activated Protein Kinase Kinases / Q000378:metabolism; D020928:Mitogen-Activated Protein Kinases / Q000378:metabolism; D008969:Molecular Sequence Data; D009154:Mutation; D016376:Oligonucleotides, Antisense; D010641:Phenotype; D010750:Phosphoproteins / Q000235:genetics / Q000378:metabolism*; D010766:Phosphorylation; D011493:Protein Kinase C / Q000737:chemistry / Q000235:genetics / Q000378:metabolism*; D051745:Protein Kinase C-delta; D021381:Protein Transport; D011518:Proto-Oncogene Proteins / Q000235:genetics / Q000378:metabolism*; D011956:Receptors, Cell Surface / Q000378:metabolism; D043562:Receptors, G-Protein-Coupled; D015398:Signal Transduction; D051153:Wnt Proteins; D014981:Xenopus; D029867:Xenopus Proteins / Q000378:metabolism; D029961:Zebrafish Proteins
D048868:Adaptor Proteins, Signal Transducing; D000072261:Dishevelled Proteins; C492040:Fzd7 protein, Xenopus; D016376:Oligonucleotides, Antisense; D010750:Phosphoproteins; D011518:Proto-Oncogene Proteins; D011956:Receptors, Cell Surface; D043562:Receptors, G-Protein-Coupled; D051153:Wnt Proteins; D029867:Xenopus Proteins; D029961:Zebrafish Proteins; D028341:Activins; D011493:Protein Kinase C; D051745:Protein Kinase C-delta; D048031:JNK Mitogen-Activated Protein Kinases; D020928:Mitogen-Activated Protein Kinases; D048688:MAP Kinase Kinase 7; C482569:MAP2K7 protein, human; D020929:Mitogen-Activated Protein Kinase Kinases