Ror-family receptor tyrosine kinases in noncanonical Wnt signaling: their implications in developmental morphogenesis and human diseases.
The Ror-family receptor tyrosine kinases (RTKs) play crucial roles in the development of various organs and tissues. In mammals, Ror2, a member of the Ror-family RTKs, has been shown to act as a receptor or coreceptor for Wnt5a to mediate noncanonical Wnt signaling. Ror2- and Wnt5a-deficient mice exhibit similar abnormalities during developmental morphogenesis, reflecting their defects in convergent extension movements and planar cell polarity, characteristic features mediated by noncanonical Wnt signaling. Furthermore, mutations within the human Ror2 gene are responsible for the genetic skeletal disorders dominant brachydactyly type B and recessive Robinow syndrome. Accumulating evidence demonstrate that Ror2 mediates noncanonical Wnt5a signaling by inhibiting the beta-catenin-TCF pathway and activating the Wnt/JNK pathway that results in polarized cell migration. In this article, we review recent progress in understanding the roles of noncanonical Wnt5a/Ror2 signaling in developmental morphogenesis and in human diseases, including heritable skeletal disorders and tumor invasion.
Minami
Yasuhiro
Y
Division of Cell Physiology, Department of Physiology and Cell Biology, Graduate School of Medicine, Kobe University, Kobe, Japan. minami@kobe-u.ac.jp
Oishi
Isao
I
Endo
Mitsuharu
M
Nishita
Michiru
M
D002465:Cell Movement / Q000502:physiology; D016764:Cell Polarity / Q000502:physiology; D018507:Gene Expression Regulation, Developmental / Q000502:physiology*; D030342:Genetic Diseases, Inborn / Q000235:genetics*; D006801:Humans; D008954:Models, Biological; D009024:Morphogenesis / Q000502:physiology*; D011518:Proto-Oncogene Proteins / Q000378:metabolism*; D057050:Receptor Tyrosine Kinase-like Orphan Receptors / Q000378:metabolism*; D015398:Signal Transduction / Q000502:physiology*; D051153:Wnt Proteins / Q000378:metabolism*; D000071818:Wnt-5a Protein
D011518:Proto-Oncogene Proteins; C085389:WNT5A protein, human; D051153:Wnt Proteins; D000071818:Wnt-5a Protein; C078717:ROR2 protein, human; D057050:Receptor Tyrosine Kinase-like Orphan Receptors