Ret Receptor: Functional Consequences of Oncogenic Rearrangements
Abstract
Ret/ptc2 is a soluble, constitutively active oncogenic protein whose gene was cloned from human papillary thyroid carcinomas. Ret/ptc2 is a chimeric protein resulting from a reciprocal chromosomal rearrangement translocation event between the cAMP-dependent protein kinase regulatory subunit type Ialpha (RIalpha) and the tyrosine kinase domain of the Ret receptor. Earlier microinjection studies showed the RIalpha dimerization domain is critical for eliciting a mitogenic response in mouse 1OT 1/2 fibroblasts. By combining results obtained from microinjection studies of Ret/ptc2 point mutants and mapping proteins identified from a yeast two-hybrid screen to a computer generated model of the Ret/ptc2 kinase core, we have previously identified specific tyrosine residues to which the SH2 domains of Grb10 and PLCgamma, the second C-terminal LIM domain of Enigma, and the PTB domain of Shc interact. From our recent characterization of the Enigma-Shc dual association with Ret/ptc2 in mouse 1OT 1/2 fibroblasts, we propose the mitogenic response elicited by Ret/ptc2 requires Enigma for proper cellular localization and utilizes the Ras pathway via the recruitment and phosphorylation of Shc. In addition to these studies, we have overexpressed and purified His6-Ret/ptc2 from the methylotrophic yeast, Pichia pastoris, to initiate extensive in vitro biochemical and biophysical characterization.
Document Details
- Document Type
- Technical Report
- Publication Date
- Oct 01, 1997
- Accession Number
- ADA340952
Entities
People
- Susan S. Taylor
Organizations
- University of California, San Diego