Transcription factor AP-2 activity is modulated by protein kinase A-mediated phosphorylation

被引:61
作者
García, MA [1 ]
Campillos, M [1 ]
Marina, A [1 ]
Valdivieso, F [1 ]
Vázquez, J [1 ]
机构
[1] Univ Autonoma Madrid, CSIC, Ctr Biol Mol Severo Ochoa, E-28049 Madrid, Spain
关键词
AP-2; cAMP; protein kinase A; APOE promoter; Alzheimer's disease;
D O I
10.1016/S0014-5793(99)00021-6
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
We recently reported that APOE promoter activity is stimulated by cAMP, this effect being mediated by factor AP-2 [Garcia et al. (1996) J. Neurosci. 16, 7550-7556]. Here, we study whether cAMP-induced phosphorylation modulates the activity of AP-2. Recombinant AP-2 was phosphorylated in vitro by protein kinase A (PKA) at Ser(239). Mutation of Ser(239) to Ala abolished in vitro phosphorylation of AP-2 by PKA, but not the DNA binding activity of AP-2. Cotransfection studies showed that PKA stimulated the effect of AP-2 on the APOE promoter, but not that of the S239A mutant, Therefore, cAMP may modulate AP-2 activity by PKA-induced phosphorylation of this factor. (C) 1999 Federation of European Biochemical Societies.
引用
收藏
页码:27 / 31
页数:5
相关论文
共 29 条
[1]   FLUORESCENCE RATIO IMAGING OF CYCLIC-AMP IN SINGLE CELLS [J].
ADAMS, SR ;
HAROOTUNIAN, AT ;
BUECHLER, YJ ;
TAYLOR, SS ;
TSIEN, RY .
NATURE, 1991, 349 (6311) :694-697
[2]  
ANDREWS DM, 1991, INT J PEPT PROT RES, V38, P469
[3]   Risk for Alzheimer's disease correlates with transcriptional activity of the APOE gene [J].
Artiga, MJ ;
Bullido, MJ ;
Frank, A ;
Sastre, I ;
Recuero, M ;
Garcia, MA ;
Lendon, CL ;
Han, SW ;
Morris, JC ;
Vázquez, J ;
Goate, A ;
Valdivieso, F .
HUMAN MOLECULAR GENETICS, 1998, 7 (12) :1887-1892
[4]   Allelic polymorphisms in the transcriptional regulatory region of apolipoprotein E gene [J].
Artiga, MJ ;
Bullido, MJ ;
Sastre, I ;
Recuero, M ;
García, MA ;
Aldudo, J ;
Vázquez, J ;
Valdivieso, F .
FEBS LETTERS, 1998, 421 (02) :105-108
[5]   A ROLE FOR APOLIPOPROTEIN-E, APOLIPOPROTEIN-A-I, AND LOW-DENSITY LIPOPROTEIN RECEPTORS IN CHOLESTEROL TRANSPORT DURING REGENERATION AND REMYELINATION OF THE RAT SCIATIC-NERVE [J].
BOYLES, JK ;
ZOELLNER, CD ;
ANDERSON, LJ ;
KOSIK, LM ;
PITAS, RE ;
WEISGRABER, KH ;
HUI, DY ;
MAHLEY, RW ;
GEBICKEHAERTER, PJ ;
IGNATIUS, MJ ;
SHOOTER, EM .
JOURNAL OF CLINICAL INVESTIGATION, 1989, 83 (03) :1015-1031
[6]   A polymorphism in the regulatory region of APOE associated with risk for Alzheimer's dementia [J].
Bullido, MJ ;
Artiga, MJ ;
Recuero, M ;
Sastre, I ;
Garcia, MA ;
Aldudo, J ;
Lendon, C ;
Han, SW ;
Morris, JC ;
Frank, A ;
Vázquez, J ;
Goate, A ;
Valdivieso, F .
NATURE GENETICS, 1998, 18 (01) :69-71
[7]   GENE DOSE OF APOLIPOPROTEIN-E TYPE-4 ALLELE AND THE RISK OF ALZHEIMERS-DISEASE IN LATE-ONSET FAMILIES [J].
CORDER, EH ;
SAUNDERS, AM ;
STRITTMATTER, WJ ;
SCHMECHEL, DE ;
GASKELL, PC ;
SMALL, GW ;
ROSES, AD ;
HAINES, JL ;
PERICAKVANCE, MA .
SCIENCE, 1993, 261 (5123) :921-923
[8]  
Garcia MA, 1996, J NEUROSCI, V16, P7550
[9]   TRANSCRIPTIONAL ACTIVATION BY MYC IS UNDER NEGATIVE CONTROL BY THE TRANSCRIPTION FACTOR AP-2 [J].
GAUBATZ, S ;
IMHOF, A ;
DOSCH, R ;
WERNER, O ;
MITCHELL, P ;
BUETTNER, R ;
EILERS, M .
EMBO JOURNAL, 1995, 14 (07) :1508-1519
[10]   CYCLIC-AMP STIMULATES SOMATOSTATIN GENE-TRANSCRIPTION BY PHOSPHORYLATION OF CREB AT SERINE-133 [J].
GONZALEZ, GA ;
MONTMINY, MR .
CELL, 1989, 59 (04) :675-680