Accession Number : ADA315785
Title : Molecular Recognition of Endocytic Codes in Receptor Tyrosine Kinases.
Descriptive Note : Annual rept. 1 Jul 94-30 Jun 96,
Corporate Author : CALIFORNIA UNIV SAN DIEGO LA JOLLA
Personal Author(s) : Wu, Rui-Yun ; Gill, Gordon
PDF Url : ADA315785
Report Date : JUL 1996
Pagination or Media Count : 50
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.
Descriptors : *PEPTIDES, *CELLS(BIOLOGY), *RECEPTOR SITES(PHYSIOLOGY), *TYROSINE, *GROWTH(PHYSIOLOGY), HUMANS, INTERACTIONS, MOLECULES, STRUCTURES, ISOLATION, TARGETS, DEOXYRIBONUCLEIC ACIDS, MUTATIONS, RECOGNITION, LIBRARIES, SENSE ORGANS, INSULIN, PHOSPHORUS TRANSFERASES.
Subject Categories : Biochemistry
Medicine and Medical Research
Distribution Statement : APPROVED FOR PUBLIC RELEASE