ORCID Profile
0000-0001-9356-1189
Current Organisations
Valparaiso University
,
University of Aberdeen
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Publisher: Wiley
Date: 19-09-2002
DOI: 10.1002/JEMT.10177
Abstract: The Eph family of receptor tyrosine kinases and their cell-presented ligands, the ephrins, are frequently overexpressed in a wide variety of cancers, including breast, small-cell lung and gastrointestinal cancers, melanomas, and neuroblastomas. In particular, one Eph family member, EphA2, is overexpressed in many cancers, including 40% of breast cancers. EphA2 can also transform breast epithelial cells in vitro to display properties commonly associated with the development of metastasis. Remarkably, the oncogenic properties of EphA2 contravene traditional dogma with regard to the oncogenic properties of a growth factor and its receptor tyrosine kinase: while stimulation of EphA2 by its ligand (ephrin-A1) results in EphA2 autophosphorylation, the stimulation reverses the oncogenic transformation. As will be discussed in this review, the apparent dependence of oncogenicity on the dephosphorylated state of EphA2 most probably reflects the unique nature of Eph signaling. In particular, oncogenecity may depend on the capacity of unactivated EphA2 to interact with a variety of signaling molecules. As well as acting in oncogenic transformation, a growing body of evidence supports the importance of the concerted actions of ephrins and Eph molecules in tumor angiogenesis. Genetic studies, using targeted mutagenesis in mice, reveal that ephrin-B1, ephrin-B2, and EphB4 are essential for the normal morphogenesis of the embryonic vasculature into a sophisticated network of arteries, veins, and capillaries. Initial studies indicate that these molecules are also angiogenic in tumors, and as such represent important new targets for the development of chemotherapeutic treatments.
Publisher: Elsevier BV
Date: 08-1995
DOI: 10.1016/0092-8674(95)90426-3
Abstract: Topographic maps with a defined spatial ordering of neuronal connections are a key feature of brain organization. Such maps are believed to develop in response to complementary position-specific labels in presynaptic and postsynaptic fields. However, the complementary labeling molecules are not known. In the well-studied visual map of retinal axons projecting to the tectum, the labels are hypothesized to be in gradients, without needing large numbers of cell-specific molecules. We recently cloned ELF-1 as a ligand for Eph family receptors. Here, RNA hybridization shows matching expression gradients for ELF-1 in the tectum and its receptor Mek4 in the retina. Binding activity detected with alkaline phosphatase fusions of ELF-1 and Mek4 also reveals gradients and provides direct evidence for molecular complementarity of gradients in reciprocal fields. ELF-1 and Mek4 may therefore play roles in retinotectal development and have properties predicted of topographic mapping labels.
Location: United Kingdom of Great Britain and Northern Ireland
Location: United States of America
No related grants have been discovered for Masaru Nakamoto.