Xenopus Pkdcc1 and Pkdcc2 Are Two New Tyrosine Kinases Involved in the Regulation of JNK Dependent Wnt/PCP Signaling Pathway.
Protein Kinase Domain Containing, Cytoplasmic (PKDCC) is a protein kinase which has been implicated in longitudinal bone growth through regulation of chondrocytes formation. Nevertheless, the mechanism by which this occurs remains unknown. Here, we identified two new members of the PKDCC family, Pkdcc1 and Pkdcc2 from Xenopus laevis. Interestingly, our knockdown experiments revealed that these two proteins are both involved on blastopore and neural tube closure during gastrula and neurula stages, respectively. In vertebrates, tissue polarity and cell movement observed during gastrulation and neural tube closure are controlled by Wnt/Planar Cell Polarity (PCP) molecular pathway. Our results showed that Pkdcc1 and Pkdcc2 promote the recruitment of Dvl to the plasma membrane. But surprisingly, they revealed different roles in the induction of a luciferase reporter under the control of Atf2 promoter. While Pkdcc1 induces Atf2 expression, Pkdcc2 does not, and furthermore inhibits its normal induction by Wnt11 and Wnt5a. Altogether our data show, for the first time, that members of the PKDCC family are involved in the regulation of JNK dependent Wnt/PCP signaling pathway.
Regenerative Medicine Program, Departamento de Ciências Biomédicas e Medicina, Universidade do Algarve, Faro, Portugal; Center for Biomedical Research (CBMR), Universidade do Algarve, Campus de Gambelas, Faro, Portugal.
Marta
M
Vitorino
Center for Biomedical Research (CBMR), Universidade do Algarve, Campus de Gambelas, Faro, Portugal.
Ana Cristina
AC
Silva
Regenerative Medicine Program, Departamento de Ciências Biomédicas e Medicina, Universidade do Algarve, Faro, Portugal; Center for Biomedical Research (CBMR), Universidade do Algarve, Campus de Gambelas, Faro, Portugal; CEDOC, NOVA Medical School/Faculdade de Ciências Médicas, Universidade Nova de Lisboa, Lisboa, Portugal.
José Manuel
JM
Inácio
CEDOC, NOVA Medical School/Faculdade de Ciências Médicas, Universidade Nova de Lisboa, Lisboa, Portugal.
José Silva
JS
Ramalho
Department of Developmental Biology and Cancer Research, Institute for Medical Research Israel-Canada, Faculty of Medicine, Hebrew University, P.O. Box 12272, Jerusalem, 91120, Israel.
Michal
M
Gur
Department of Developmental Biology and Cancer Research, Institute for Medical Research Israel-Canada, Faculty of Medicine, Hebrew University, P.O. Box 12272, Jerusalem, 91120, Israel.
Abraham
A
Fainsod
Institute of Human Genetics, University of Heidelberg, Heidelberg, Germany.
Herbert
H
Steinbeisser
Regenerative Medicine Program, Departamento de Ciências Biomédicas e Medicina, Universidade do Algarve, Faro, Portugal; Center for Biomedical Research (CBMR), Universidade do Algarve, Campus de Gambelas, Faro, Portugal; CEDOC, NOVA Medical School/Faculdade de Ciências Médicas, Universidade Nova de Lisboa, Lisboa, Portugal.
José António
JA
Belo
D048868:Adaptor Proteins, Signal Transducing / Q000378:metabolism; D000818:Animals; D002465:Cell Movement; D016764:Cell Polarity; D003001:Cloning, Molecular / Q000379:methods; D000072261:Dishevelled Proteins; D018507:Gene Expression Regulation, Developmental; D020935:MAP Kinase Signaling System; D010750:Phosphoproteins / Q000378:metabolism; D011505:Protein-Tyrosine Kinases / Q000235:genetics / Q000378:metabolism*; D060449:Wnt Signaling Pathway; D029867:Xenopus Proteins / Q000235:genetics / Q000378:metabolism*; D014982:Xenopus laevis / Q000196:embryology* / Q000235:genetics / Q000378:metabolism*
D048868:Adaptor Proteins, Signal Transducing; C000606586:DVL1 protein, Xenopus; D000072261:Dishevelled Proteins; D010750:Phosphoproteins; D029867:Xenopus Proteins; C000607563:Pkdcc.1 protein, Xenopus; C000607564:Pkdcc.2 protein, Xenopus; D011505:Protein-Tyrosine Kinases