Expression and function of the Ror-family receptor tyrosine kinases during development: lessons from genetic analyses of nematodes, mice, and humans.

Abstract

Receptor tyrosine kinases (RTKs) play crucial roles in various developmental processes. Ror-family RTKs are characterized by the intracellular tyrosine kinase domains, highly related to those of the Trk-family RTKs, and by the extracellular Frizzled-like cysteine-rich domains (CRDs) and Kringle domains. Rors are evolutionally conserved among Caenorhabditis elegans, Aplysia, Drosophila melanogaster, Xenopus, mice, and humans. In D. melanogaster and mammals, pairs of structurally related Rors are found, while a single Ror protein is identified in C. elegans or Aplysia. In Aplysia and D. melanogaster, Rors are expressed exclusively in developing nervous systems. On the other hand, rather widespread expression of Rors was observed in C. elegans and mammals. Mutations in Ror of C. elegans cause inappropriate axon outgrowth as well as defects in cell migration and asymmetric cell division. It has also been reported that the nematode Ror possesses kinase-dependent and kinase-independent functions. Mouse Rors, Ror1, and Ror2, are expressed mainly in migrating neural crest cells and mesenchymal cells, and Ror2-deficient mice exhibit skeletal abnormalities and ventricular septal defects in the heart. Although Ror1-deficient mice exhibit no apparent skeletal or cardiac abnormalities, Ror1/Ror2 double mutant mice show markedly enhanced skeletal and cardiac abnormalities compared with Ror2 mutant mice, indicating genetic interaction of Ror1 and Ror2. In humans, mutations within Ror2 have been found in two genetic skeletal disorders, recessive Robinow syndrome and dominant Brachydactyly type B (BDB), further emphasizing critical functions of Ror2 during developmental morphogenesis. In this article, we also discuss the signaling machinery mediated by Ror-family RTKs with a particular emphasis on our recent structure-function analyses of Ror-family RTKs.

• Authors: Akinori Yoda, Isao Oishi, Yasuhiro Minami
• Journal: Journal of receptor and signal transduction research (J Recept Signal Transduct Res) Vol. 23 Issue 1 Pg. 1-15 (Feb 2003) ISSN: 1079-9893 [Print] England
• PMID: 12680586 (Publication Type: Journal Article, Research Support, Non-U.S. Gov't, Review)

Chemical References

• Caenorhabditis elegans Proteins
• Receptors, Cell Surface
• CAM-1 protein, C elegans
• ROR2 protein, human
• Receptor Protein-Tyrosine Kinases
• Receptor Tyrosine Kinase-like Orphan Receptors
• Ror1 protein, mouse
• Ror2 protein, mouse

Topics

• Amino Acid Sequence
• Animals
• Caenorhabditis elegans (enzymology, genetics, growth & development)
• Caenorhabditis elegans Proteins
• Gene Expression Regulation, Developmental
• Gene Expression Regulation, Enzymologic
• Genes, Helminth
• Humans
• Mice
• Mice, Mutant Strains
• Molecular Structure
• Mutation
• Nervous System (embryology)
• Phenotype
• Receptor Protein-Tyrosine Kinases (chemistry, genetics, physiology)
• Receptor Tyrosine Kinase-like Orphan Receptors
• Receptors, Cell Surface (genetics)
• Sequence Homology, Amino Acid
• Signal Transduction