Biochemical characterization of various catalytic complexes of the brain platelet-activating factor acetylhydrolase

被引:48
作者
Manya, H [1 ]
Aoki, J [1 ]
Kato, H [1 ]
Ishii, J [1 ]
Hino, S [1 ]
Arai, H [1 ]
Inoue, K [1 ]
机构
[1] Univ Tokyo, Grad Sch Pharmaceut Sci, Dept Hlth Chem, Bunkyo Ku, Tokyo 113, Japan
关键词
D O I
10.1074/jbc.274.45.31827
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
Brain intracellular platelet-activating factor acetylhydrolase (PAF-AH) isoform I is a member of a family of complex enzymes composed of mutually homologous alpha(1) and alpha(2) subunits, both of which account for catalytic activity, and the beta subunit. We previously demonstrated that the expression of one catalytic subunit, alpha(1), is developmentally regulated, resulting in a switching of the catalytic complex from alpha(1)/alpha(2) to alpha(2)/alpha(2) during brain development (Manya, H., Aoki, J., Watanabe, M., Adachi, T., Asou, H., Inoue, Y., Arai, H., and Inoue, K. (1998) J. Biol. Chem. 273, 18567-18572). In this study, we explored the biochemical differences in three possible catalytic dimers, alpha(1)/alpha(1), alpha(1)/alpha(2), and alpha(2)/alpha(2). The alpha(2)/alpha(2) homodimer exhibited different substrate specificity from the alpha(1)/alpha(1) homodimer and the alpha(1)/alpha(2) heterodimer, both of which showed similar substrate specificity. The alpha(2)/alpha(2) homodimer hydrolyzed PAF and 1-O-alkyl-2-acetyl-sn-glycero-3-phosphorylethanolamine (AAGPE) most efficiently among 1-O-alkyl-2-acetyl-phospholipids. In contrast, both alpha(1)/alpha(1) and alpha(1)/alpha(2) hydrolyzed 1-O-alkyl-2-acetyl-sn-glycero-3-phosphoric acid more efficiently than PAF. AAGPE was the poorest substrate for these enzymes. The beta subunit bound to all three catalytic dimers but modulated the enzyme activity in a catalytic dimer composition-dependent manner. The beta subunit strongly accelerated the enzyme activity of the alpha(2)/alpha(2) homodimer but rather suppressed the activity of the alpha(1)/alpha(1) homodimer and had little effect on that of the alpha(1)/alpha(2) heterodimer. The (His(149) to Arg) mutant beta, which has been recently identified in isolated lissencephaly sequence patients, lost the ability to either associate with the catalytic complexes or modulate their enzyme activity. The enzyme activity of PAF-AH isoform I may be regulated in multiple ways by switching the composition of the catalytic subunit and by manipulating the beta subunit.
引用
收藏
页码:31827 / 31832
页数:6
相关论文
共 15 条
[1]   Platelet-activating factor acetylhydrolase expression and activity suggest a link between neuronal migration and platelet-activating factor [J].
Albrecht, U ;
AbuIssa, R ;
Ratz, B ;
Hattori, M ;
Aoki, J ;
Arai, H ;
Inoue, K ;
Eichele, G .
DEVELOPMENTAL BIOLOGY, 1996, 180 (02) :579-593
[2]   Enzymes of platelet activating factor synthesis in brain [J].
Baker, RR .
NEUROCHEMICAL RESEARCH, 1995, 20 (11) :1345-1351
[3]   PURIFICATION AND CHARACTERIZATION OF PLATELET-ACTIVATING-FACTOR ACETYLHYDROLASE-II FROM BOVINE LIVER CYTOSOL [J].
HATTORI, K ;
HATTORI, M ;
ADACHI, H ;
TSUJIMOTO, M ;
ARAI, H ;
INOUE, K .
JOURNAL OF BIOLOGICAL CHEMISTRY, 1995, 270 (38) :22308-22313
[4]   Cloning and expression of a cDNA encoding the beta-subunit (30-kDa subunit) of bovine brain platelet-activating factor acetylhydrolase [J].
Hattori, M ;
Adachi, H ;
Aoki, J ;
Tsujimoto, M ;
Arai, H ;
Inoue, K .
JOURNAL OF BIOLOGICAL CHEMISTRY, 1995, 270 (52) :31345-31352
[5]  
HATTORI M, 1993, J BIOL CHEM, V268, P18748
[6]  
HATTORI M, 1994, J BIOL CHEM, V269, P23150
[7]   MILLER-DIEKER LISSENCEPHALY GENE ENCODES A SUBUNIT OF BRAIN PLATELET-ACTIVATING-FACTOR [J].
HATTORI, M ;
ADACHI, H ;
TSUJIMOTO, M ;
ARAI, H ;
INOUE, K .
NATURE, 1994, 370 (6486) :216-218
[8]   Brain acetylhydrolase that inactivates platelet-activating factor is a G-protein-like trimer [J].
Ho, YS ;
Swenson, L ;
Derewenda, U ;
Serre, L ;
Wei, YY ;
Dauter, Z ;
Hattori, M ;
Adachi, T ;
Aoki, J ;
Arai, H ;
Inoue, K ;
Derewenda, ZS .
NATURE, 1997, 385 (6611) :89-93
[9]  
LEE TC, 1992, J BIOL CHEM, V267, P19992
[10]  
LO NC, 1997, HUM MOL GENET, V6, P157