ISOLATION AND CHARACTERIZATION OF APLP2 ENCODING A HOMOLOG OF THE ALZHEIMERS ASSOCIATED AMYLOID BETA-PROTEIN PRECURSOR

被引:341
作者
WASCO, W
GURUBHAGAVATULA, S
DPARADIS, M
ROMANO, DM
SISODIA, SS
HYMAN, BT
NEVE, RL
TANZI, RE
机构
[1] MASSACHUSETTS GEN HOSP, DEPT NEUROL, BOSTON, MA 02115 USA
[2] MCLEAN HOSP, MAILMAN RES CTR, BELMONT, MA 02178 USA
[3] JOHNS HOPKINS UNIV, SCH MED, DEPT PATHOL, BALTIMORE, MD 21205 USA
[4] JOHNS HOPKINS UNIV, SCH MED, NEUROPATHOL LAB, BALTIMORE, MD 21205 USA
关键词
D O I
10.1038/ng0993-95
中图分类号
Q3 [遗传学];
学科分类号
071007 ; 090102 ;
摘要
Familial Alzheimer's disease (FAD) is a genetically heterogeneous disorder that includes a rare early-onset form linked to mutations in the amyloid b protein precursor (APP) gene. Clues to the function of APP derive from the recent finding that it is a member of a highly conserved protein family that includes the mammalian amyloid precursor-like protein (APLP1) gene which maps to the same general region of human chromosome 19 linked to late-onset FAD. Here we report the isolation of the human APLP2 gene. We show that APLP2 is a close relative of APP and exhibits a very similar pattern of expression in the brain and throughout the body. Like APP, APLP2 contains a cytoplasmic domain predicted to couple with the GTP-binding protein G(o) indicating that it may be an additional cell surface activator of this G protein.
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页码:95 / 100
页数:6
相关论文
共 51 条
[11]   A G0-LIKE PROTEIN IN DROSOPHILA-MELANOGASTER AND ITS EXPRESSION IN MEMORY MUTANTS [J].
GUILLEN, A ;
JALLON, JM ;
FEHRENTZ, JA ;
PANTALONI, C ;
BOCKAERT, J ;
HOMBURGER, V .
EMBO JOURNAL, 1990, 9 (05) :1449-1455
[12]   AMYLOID BETA-PEPTIDE IS PRODUCED BY CULTURED-CELLS DURING NORMAL METABOLISM [J].
HAASS, C ;
SCHLOSSMACHER, MG ;
HUNG, AY ;
VIGOPELFREY, C ;
MELLON, A ;
OSTASZEWSKI, BL ;
LIEBERBURG, I ;
KOO, EH ;
SCHENK, D ;
TEPLOW, DB ;
SELKOE, DJ .
NATURE, 1992, 359 (6393) :322-325
[13]   TARGETING OF CELL-SURFACE BETA-AMYLOID PRECURSOR PROTEIN TO LYSOSOMES - ALTERNATIVE PROCESSING INTO AMYLOID-BEARING FRAGMENTS [J].
HAASS, C ;
KOO, EH ;
MELLON, A ;
HUNG, AY ;
SELKOE, DJ .
NATURE, 1992, 357 (6378) :500-503
[14]   NONISOTOPIC INSITU HYBRIDIZATION OF AMYLOID BETA-PROTEIN PRECURSOR IN ALZHEIMERS-DISEASE - EXPRESSION IN NEUROFIBRILLARY TANGLE BEARING NEURONS AND IN THE MICROENVIRONMENT SURROUNDING SENILE PLAQUES [J].
HYMAN, BT ;
WENNIGER, JJ ;
TANZI, RE .
MOLECULAR BRAIN RESEARCH, 1993, 18 (03) :253-258
[15]   A NOVEL SPECIES-SPECIFIC RNA RELATED TO ALTERNATIVELY SPLICED AMYLOID PRECURSOR PROTEIN MESSENGER-RNAS [J].
JACOBSEN, JS ;
MUENKEL, HA ;
BLUME, AJ ;
VITEK, MP .
NEUROBIOLOGY OF AGING, 1991, 12 (05) :575-583
[16]   THE PRECURSOR OF ALZHEIMERS-DISEASE AMYLOID-A4 PROTEIN RESEMBLES A CELL-SURFACE RECEPTOR [J].
KANG, J ;
LEMAIRE, HG ;
UNTERBECK, A ;
SALBAUM, JM ;
MASTERS, CL ;
GRZESCHIK, KH ;
MULTHAUP, G ;
BEYREUTHER, K ;
MULLERHILL, B .
NATURE, 1987, 325 (6106) :733-736
[17]   NOVEL PRECURSOR OF ALZHEIMERS-DISEASE AMYLOID PROTEIN SHOWS PROTEASE INHIBITORY ACTIVITY [J].
KITAGUCHI, N ;
TAKAHASHI, Y ;
TOKUSHIMA, Y ;
SHIOJIRI, S ;
ITO, H .
NATURE, 1988, 331 (6156) :530-532
[18]  
KONIG G, 1992, J BIOL CHEM, V267, P19804
[19]   HUMAN AMYLOID PRECURSOR PROTEIN AMELIORATES BEHAVIORAL DEFICIT OF FLIES DELETED FOR APPL GENE [J].
LUO, LQ ;
TULLY, T ;
WHITE, K .
NEURON, 1992, 9 (04) :595-605
[20]   IDENTIFICATION, SECRETION, AND NEURAL EXPRESSION OF APPL, A DROSOPHILA PROTEIN SIMILAR TO HUMAN AMYLOID PROTEIN-PRECURSOR [J].
LUO, LQ ;
MARTINMORRIS, LE ;
WHITE, K .
JOURNAL OF NEUROSCIENCE, 1990, 10 (12) :3849-3861