The low molecular weight tyrosine phosphatase, HCPTP-A, has recently been discovered as having oncogenic characteristics. The oncogenic character of this particular phosphatase has been linked to the ephrin receptor tyrosine kinases, B2, B1 and A2, which in turn have been well documented as playing a vital role in the development of vascular networks (""""""""vascular mimicry"""""""") in breast, lung, and prostate cancers. The exact mode of interaction between HCPTP-A and the ephrin receptors remain unknown. Two sites of interactions on the ephrin receptors for HCPTP-A have been postulated: the cystosolic juxtamembrane region and SAM domain. In order to investigate whether or not the SAM domain or the juxtamembrane regions are potential substrates for HCPTP-A, phosphopeptides have been created from the putative sites of interaction. The kinetic characterization of the derived peptides for HCPTP-A, the analysis of which residues of the peptides contribute most to its binding kinetics through an alanine scanning method, and the structural analysis of the peptides and HCPTP-A via x-ray crystallography will be implemented to elucidate whether or not there is a preferential mode of interaction between the ephrin receptors and HCPTP-A. ? ?
| Balasubramaniam, Deepa; Paul, Lake N; Homan, Kristoff T et al. (2011) Specificity of HCPTP variants toward EphA2 tyrosines by quantitative selected reaction monitoring. Protein Sci 20:1172-81 |
