Abstract
Tek/Tie2 is an endothelial cell-specific receptor tyrosine kinase that has been shown to play a role in vascular development of the mouse. Targeted mutagenesis of both Tek and its agonistic ligand, Angiopoietin-1, result in embryonic lethality, demonstrating that the signal transduction pathway(s) mediated by this receptor are crucial for normal embryonic development. In an attempt to identify downstream signaling partners of the Tek receptor, we have used the yeast two-hybrid system to identify phosphotyrosine-dependent interactions. Using this approach, we have identified a novel docking molecule called Dok-R, which has sequence and structural homology to p62dok and IRS-3. Mapping of the phosphotyrosine-interaction domain within Dok-R shows that Dok-R interacts with Tek through a PTB domain. Dok-R is coexpressed with Tek in a number of endothelial cell lines. We show that coexpression of Dok-R with activated Tek results in tyrosine phosphorylation of Dok-R and that rasGAP and Nck coimmunoprecipitate with phosphorylated Dok-R. Furthermore, Dok-R is constitutively bound to Crk presumably through the proline rich tail of Dok-R. The cloning of Dok-R represents the first downstream substrate of the activated Tek receptor, and suggests that Tek can signal through a multitude of pathways.
This is a preview of subscription content, access via your institution
Access options
Subscribe to this journal
Receive 50 print issues and online access
$259.00 per year
only $5.18 per issue
Buy this article
- Purchase on Springer Link
- Instant access to full article PDF
Prices may be subject to local taxes which are calculated during checkout
Similar content being viewed by others
Author information
Authors and Affiliations
Rights and permissions
About this article
Cite this article
Jones, N., Dumont, D. The Tek/Tie2 receptor signals through a novel Dok-related docking protein, Dok-R. Oncogene 17, 1097–1108 (1998). https://doi.org/10.1038/sj.onc.1202115
Received:
Revised:
Accepted:
Published:
Issue Date:
DOI: https://doi.org/10.1038/sj.onc.1202115
Keywords
This article is cited by
-
Downstream of tyrosine kinase/docking protein 6, as a novel substrate of tropomyosin-related kinase C receptor, is involved in neurotrophin 3-mediated neurite outgrowth in mouse cortex neurons
BMC Biology (2010)
-
Targeting the ANGPT–TIE2 pathway in malignancy
Nature Reviews Cancer (2010)
-
Nck adapter proteins: functional versatility in T cells
Cell Communication and Signaling (2009)
-
Detection of Homo- or Hetero-Association of Doks by Fluorescence Resonance Energy Transfer in Living Cells
Molecular Imaging and Biology (2009)
-
The role of the Angiopoietins in vascular morphogenesis
Angiogenesis (2009)