Specificity of LIM domain interactions with receptor tyrosine kinases

被引:83
作者
Wu, RY
Durick, K
Zhou, SY
Cantley, LC
Taylor, SS
Gill, GN
机构
[1] UNIV CALIF SAN DIEGO, DEPT BIOL, LA JOLLA, CA 92093 USA
[2] UNIV CALIF SAN DIEGO, DEPT MED, LA JOLLA, CA 92093 USA
[3] UNIV CALIF SAN DIEGO, DEPT CHEM & BIOCHEM, LA JOLLA, CA 92093 USA
[4] HARVARD UNIV, SCH MED, CAMBRIDGE, MA 02115 USA
关键词
D O I
10.1074/jbc.271.27.15934
中图分类号
Q5 [生物化学]; Q7 [分子生物学];
学科分类号
071010 ; 081704 ;
摘要
LIM domains, Cys-rich motifs containing approximately 50 amino acids found in a variety of proteins, are proposed to direct protein protein interactions, To identify structural targets recognized by LIM domains, we have utilized random peptide library selection, the yeast two-hybrid system, and glutathione S-transferase fusions, Enigma contains three LIM domains within its carboxyl terminus and LIM3 of Enigma specifically recognizes active but not mutant endocytic codes of the insulin receptor (InsR) (Wu, R Y,, and Gill, Gr, N, (1994) J. Biol, Chem. 269, 2508-25090). Interaction of two random peptide libraries nifh glutathione S-transferase-LIM3 of Enigma indicated specific binding to Gly-Pro-Hyd-Gly-Pro-Hyd-Tyr-Ala corresponding to the major endocytic code of InsR Peptide competition demonstrated that both Pro and Tyr residues were required for specific interaction of InsR with Enigma, In contrast to LIM3 of Enigma binding to InsR, LIM2 of Enigma associated specifically with the receptor tyrosine kinase, Ret. Ret was specific for LIM2 of Enigma and did not bind other LIM domains tested, Mutational analysis indicated that the residues responsible for binding to Enigma were localized to the carboxyl-terminal 61 amino acids of Ret, A peptide corresponding to the carboxyl-terminal 20 amino acids of Ret dissociated Enigma and Ret complexes, while a mutant that changed Asn-Lys-Leu-Tyr in the peptide to Ala-Lys-Leu-Ala or a peptide corresponding to exon16 of InsR failed to disrupt the complexes, indicating the Asn-Lys-Leu-Tyr sequence of Ret is essential to the recognition moth for LIM2 of Enigma, We conclude that LIM domains of Enigma recognize tyrosine-containing motifs with specificity residing in both the LIM domains and in the target structures.
引用
收藏
页码:15934 / 15941
页数:8
相关论文
共 46 条
  • [21] INSULIN GENE ENHANCER BINDING-PROTEIN ISL-1 IS A MEMBER OF A NOVEL CLASS OF PROTEINS CONTAINING BOTH A HOMEODOMAIN AND A CYS-HIS DOMAIN
    KARLSSON, O
    THOR, S
    NORBERG, T
    OHLSSON, H
    EDLUND, T
    [J]. NATURE, 1990, 344 (6269) : 879 - 882
  • [22] PTB DOMAIN BINDING TO SIGNALING PROTEINS THROUGH A SEQUENCE MOTIF CONTAINING PHOSPHOTYROSINE
    KAVANAUGH, WM
    TURCK, CW
    WILLIAMS, LT
    [J]. SCIENCE, 1995, 268 (5214) : 1177 - 1179
  • [23] A NOVEL DI-LEUCINE MOTIF AND A TYROSINE-BASED MOTIF INDEPENDENTLY MEDIATE LYSOSOMAL TARGETING AND ENDOCYTOSIS OF CD3 CHAINS
    LETOURNEUR, F
    KLAUSNER, RD
    [J]. CELL, 1992, 69 (07) : 1143 - 1157
  • [24] Oncogenic RET receptors display different autophosphorylation sites and substrate binding specificities
    Liu, X
    Vega, QC
    Decker, RA
    Pandey, A
    Worby, CA
    Dixon, JE
    [J]. JOURNAL OF BIOLOGICAL CHEMISTRY, 1996, 271 (10) : 5309 - 5312
  • [25] STRUCTURAL REQUIREMENTS AND SEQUENCE MOTIFS FOR POLARIZED SORTING AND ENDOCYTOSIS OF LDL-RECEPTORS AND FC-RECEPTORS IN MDCK CELLS
    MATTER, K
    YAMAMOTO, EM
    MELLMAN, I
    [J]. JOURNAL OF CELL BIOLOGY, 1994, 126 (04) : 991 - 1004
  • [26] THE LIM MOTIF DEFINES A SPECIFIC ZINC-BINDING PROTEIN DOMAIN
    MICHELSEN, JW
    SCHMEICHEL, KL
    BECKERLE, MC
    WINGE, DR
    [J]. PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES OF THE UNITED STATES OF AMERICA, 1993, 90 (10) : 4404 - 4408
  • [27] MIZUNO K, 1994, ONCOGENE, V9, P1605
  • [28] GERM-LINE MUTATIONS OF THE RET PROTOONCOGENE IN MULTIPLE ENDOCRINE NEOPLASIA TYPE-2A
    MULLIGAN, LM
    KWOK, JBJ
    HEALEY, CS
    ELSDON, MJ
    ENG, C
    GARDNER, E
    LOVE, DR
    MOLE, SE
    MOORE, JK
    PAPI, L
    PONDER, MA
    TELENIUS, H
    TUNNACLIFFE, A
    PONDER, BAJ
    [J]. NATURE, 1993, 363 (6428) : 458 - 460
  • [29] PROTEIN MODULES AND SIGNALING NETWORKS
    PAWSON, T
    [J]. NATURE, 1995, 373 (6515) : 573 - 580
  • [30] STRUCTURE OF THE CARBOXY-TERMINAL LIM DOMAIN FROM THE CYSTEINE-RICH PROTEIN CRP
    PEREZALVARADO, GC
    MILES, C
    MICHELSEN, JW
    LOUIS, HA
    WINGE, DR
    BECKERLE, MC
    SUMMERS, MF
    [J]. NATURE STRUCTURAL BIOLOGY, 1994, 1 (06): : 388 - 398