Molecular Recognition of Endocytic Codes in Receptor Tyrosine Kinases.
Abstract
Enigma, isolated based on interaction with the human insulin receptor (InsR) using a yeast two-hybrid system, contains three LIM domains within its carboxyl terminus. The carboxyl LIM domain (LIM3) specifically recognizes the endocytic codes of InsR. Interaction of two random peptide libraries indicates the specific binding of Gly-Pro-Hyr-Gly-Pro-Hyr-Tyr/Phe corresponding to the major endocytic code of InsR. The ability of LIM3 of Enigma to recognize the endocytic codes of InsR fulfills the first property of the endocytic mechanism. In contrast to LIM3 of Enigma binding to InsR, LIM2 of Enigma associates specifically with the tyrosine kinase receptor Ret. Mutational analysis indicated that Tyr(586) at the carboxyl terminus of Ret is essential for the Ret and Enigma interaction. Mutations of Ret/ptc2 which fail to interact with Enigma also lose their ability to stimulate mitogenic signaling. Co-expression of LIM domains of Enigma blocked Ret/ptc2 stimulated DNA synthesis, indicating that Enigma is involved in the mitogenic signaling of Ret. These studies have indicated that two LIM domains of Enigma can interact with two receptor tyrosine kinases through tyrosine-based motifs with specificity residing in both the LIM domains and in the target structures.
Document Details
- Document Type
- Technical Report
- Publication Date
- Jul 01, 1996
- Accession Number
- ADA315785
Entities
People
- Gordon Gill
- Rui-yun Wu
Organizations
- University of California, San Diego