Accession Number:

ADA361697

Title:

Ret Receptor: Functional Consequences of Oncogenic Rearrangements

Descriptive Note:

Final rept. 15 Sep 94-14 Sep 98

Corporate Author:

CALIFORNIA UNIV SAN DIEGO LA JOLLA

Personal Author(s):

• Taylor, Susan S.

Report Date:

1998-10-01

Pagination or Media Count:

44.0

Abstract:

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.

Descriptors:

• *ONCOGENIC VIRUSES
• *BREAST CANCER
• PEPTIDES
• PROTEINS
• THYROID GLAND
• GENES
• CLONES
• DIMERS
• EPIDERMIS
• INSULIN
• TYROSINE
• GROWTH(PHYSIOLOGY)
• PHOSPHORYLATION
• TRANSLOCATION
• PHOSPHORUS TRANSFERASES
• METASTASIS

Subject Categories:

• Biochemistry
• Genetic Engineering and Molecular Biology
• Medicine and Medical Research

Distribution Statement:

APPROVED FOR PUBLIC RELEASE