Characterization of Dok-R-mediated cell migration downstream of the receptor tyrosine kinase, Tek/Tie2.
Published: 2004
Language: eng
Number of pages: 65
Description: Tek/Tie2 is an endothelial cell receptor tyrosine kinase that induces cell migration upon Angiopoietin-1 (Ang1) stimulation. In conjunction with a phosphorylation state-specific antibody, a site-directed mutagenesis approach that mutated tyrosine residues on Tek was used that identified a unique interaction motif on Tek containing tyrosine residue 1106, an Ang1-dependent autophosphorylation site, which mediates binding to the phosphotyrosine binding (PTB) domain of the downstream of kinase-related (Dok-R) docking protein, leading to Dok-R phosphorylation. The pleckstrin homology (PH) domain of Dok-R further contributes to Tek binding in a phosphatidylinositol (PI)-3 kinase-dependent manner. A Tek mutant lacking tyrosine residue 1106 interferes with Dok-R phosphorylation in response to Ang1 in endothelial cells and cannot restore the migration potential of endothelial cells derived from mice lacking Tek. Together, these findings show that tyrosine residue 1106 on Tek is critical for coupling downstream cell migration signal transduction pathways with Angl stimulation in endothelial cells.
Notes: Adviser:  Daniel J. Dumont.

Thesis (M.Sc.)--University of Toronto, 2004.

Electronic version licensed for access by U. of T. users.

Source: Masters Abstracts International, Volume: 43-03, page: 0782.

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