Accession Number : ADA299279

Title :   Molecular Recognition of Endocytic Codes in Receptor Tyrosine Kinases.

Descriptive Note : Annual rept. 1 Jul 94-30 Jun 95,

Corporate Author : CALIFORNIA UNIV SAN DIEGO LA JOLLA

Personal Author(s) : Wu, Rui-Yun ; Gill, Gordon N.

PDF Url : ADA299279

Report Date : 22 JUL 1995

Pagination or Media Count : 10

Abstract : Proliferation of breast cancer cells is controlled by interaction of peptide growth factors with their cell surface receptors. The major attenuation mechanism for signaling involves ligand-induced internalization and down regulation of receptors, a process dependent on both intrinsic tyrosine kinase activity and specific endocytic codes. To determine mechanisms through which cells recognize this information, we utilized exon 16 of insulin receptor (InsR) in the two-hybrid system to isolate a novel protein, Enigma which contains three LIM domains within its carboxyl terminus. Mutational analyses indicated that the carboxyl terminal LIM domain of Enigma specifically recognized active but not inactive endocytic codes in InsR. Enigma failed to interact with the fragments of IGFl-R, LDLR, TfR and EGFR that contain endocytic codes. Further specificity was indicated by failure of other LIM domains to interact with exon 16 of InsR. Interestingly LIM2 of Enigma specifically recognized a distinct receptor tyrosine kinase, the endocytic code of IGFl-R was recognized by a LIM domain of Zyxin. We conclude that LIM domains recognize proteins through interaction with an exposed tyrosine located in tight turns. Variations in the sequence of tight turns and of LIM domains provide specificity for protein-protein interactions.

Descriptors :   *PEPTIDES, *GROWTH(GENERAL), *CELLS(BIOLOGY), *RECEPTOR SITES(PHYSIOLOGY), *TYROSINE, EXPOSURE(GENERAL), INTERACTIONS, MOLECULES, PROTEINS, RECEIVERS, ATTENUATION, RECOGNITION, REGULATIONS, SENSE ORGANS, INSULIN, PHOSPHORUS TRANSFERASES.

Subject Categories : Biochemistry
      Medicine and Medical Research

Distribution Statement : APPROVED FOR PUBLIC RELEASE