Ret Receptor: Functional Consequences of Oncogenic Rearrangements
Final rept. 15 Sep 94-14 Sep 98
CALIFORNIA UNIV SAN DIEGO LA JOLLA
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The retptc2 gene was cloned from human papillary thyroid carcinomas, and is the product of a reciprocal chromosomal rearrangement, translocation event between the cAMP dependent protein kinase regulatory subunit I alpha RI alpha and the tyrosine kinase domain of the Ret receptor. Retptc2 is a dimer which is autophosphorylated, soluble, and constitutively active. We generated a computer model of the Retptc2 kinase domain, expressed and purified Retptc2, developed a kinase assay to test a variety of peptide substrates and a microinjection assay to compare the structure function relationship of Retptc2 mutants. A number of tyrosine residues within the Retptc2 kinase domain as well as the RI alpha dimerization domain are critical for eliciting a mitogenic response.
- Genetic Engineering and Molecular Biology
- Medicine and Medical Research