A 70 amino acid region within the semaphorin domain activates specific cellular response of semaphorin family members

被引:131
作者
Koppel, AM [1 ]
Feiner, L [1 ]
Kobayashi, H [1 ]
Raper, JA [1 ]
机构
[1] UNIV PENN,SCH MED,DEPT NEUROSCI,PHILADELPHIA,PA 19104
基金
美国国家卫生研究院;
关键词
D O I
10.1016/S0896-6273(00)80369-4
中图分类号
Q189 [神经科学];
学科分类号
071006 ;
摘要
The semaphorin family contains secreted and transmembrane signaling proteins that function in the nervous, immune, and cardiovascular systems. Chick collapsin-1 is a repellent for specific growth cones. Two other secreted members of the semaphorin family, collapsin-2 and -3, are structurally similar to collapsin-1 but have different biological activities. Semaphorins contain a 500 amino acid family signature semaphorin domain. We show in this study that (1) the semaphorin domain of collapsin-1 is both necessary and sufficient for biological activity, (2) the semaphorin domain contains a 70 amino acid region that specifies the biological activity of the three family members, and (3) the positively charged carboxy terminus potentiates activity without affecting specificity. We propose that semaphorins interact with their receptors through two independent binding sites: one that mediates the biological response and one that potentiates it.
引用
收藏
页码:531 / 537
页数:7
相关论文
共 19 条
  • [1] Semaphorin III Is needed for normal patterning and growth of nerves, bones and heart
    Behar, O
    Golden, JA
    Mashimo, H
    Schoen, FJ
    Fishman, MC
    [J]. NATURE, 1996, 383 (6600) : 525 - 528
  • [2] IDENTIFICATION AND CLONING OF ELF-1, A DEVELOPMENTALLY EXPRESSED LIGAND FOR THE MEK4 AND SEK RECEPTOR TYROSINE KINASES
    CHENG, HJ
    FLANAGAN, JG
    [J]. CELL, 1994, 79 (01) : 157 - 168
  • [3] Secreted chick semaphorins bind recombinant neuropilin with similar affinities but bind different subsets of neurons in situ
    Feiner, L
    Koppel, AM
    Kobayashi, H
    Raper, JA
    [J]. NEURON, 1997, 19 (03) : 539 - 545
  • [4] Human CD100, a novel leukocyte semaphorin that promotes B-cell aggregation and differentiation
    Hall, KT
    Boumsell, L
    Schultze, JL
    Boussiotis, VA
    Dorfman, DM
    Cardoso, AA
    Bensussan, A
    Nadler, LM
    Freeman, GJ
    [J]. PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES OF THE UNITED STATES OF AMERICA, 1996, 93 (21) : 11780 - 11785
  • [5] ACTIVATION SIGNALS ARE DELIVERED THROUGH 2 DISTINCT EPITOPES OF CD100, A UNIQUE 150-KDA HUMAN LYMPHOCYTE SURFACE-STRUCTURE PREVIOUSLY DEFINED BY BB18-MAB
    HEROLD, C
    BISMUTH, G
    BENSUSSAN, A
    BOUMSELL, L
    [J]. INTERNATIONAL IMMUNOLOGY, 1995, 7 (01) : 1 - 8
  • [6] CHIMERIC MOLECULES WITH MULTIPLE NEUROTROPHIC ACTIVITIES REVEAL STRUCTURAL ELEMENTS DETERMINING THE SPECIFICITIES OF NGF AND BDNF
    IBANEZ, CF
    EBENDAL, T
    PERSSON, H
    [J]. EMBO JOURNAL, 1991, 10 (08) : 2105 - 2110
  • [7] DISRUPTION OF THE LOW AFFINITY RECEPTOR-BINDING SITE IN NGF ALLOWS NEURONAL SURVIVAL AND DIFFERENTIATION BY BINDING TO THE TRK GENE-PRODUCT
    IBANEZ, CF
    EBENDAL, T
    BARBANY, G
    MURRAYRUST, J
    BLUNDELL, TL
    PERSSON, H
    [J]. CELL, 1992, 69 (02) : 329 - 341
  • [8] KOBAYASHI H, 1997, IN PRESS J NEUROSCI, V17
  • [9] THE SEMAPHORIN GENES ENCODE A FAMILY OF TRANSMEMBRANE AND SECRETED GROWTH CONE GUIDANCE MOLECULES
    KOLODKIN, AL
    MATTHES, DJ
    GOODMAN, CS
    [J]. CELL, 1993, 75 (07) : 1389 - 1399
  • [10] INTERSPECIES MOLECULAR CHIMERAS OF KIT HELP DEFINE THE BINDING-SITE OF THE STEM-CELL FACTOR
    LEV, S
    BLECHMAN, J
    NISHIKAWA, SI
    GIVOL, D
    YARDEN, Y
    [J]. MOLECULAR AND CELLULAR BIOLOGY, 1993, 13 (04) : 2224 - 2234