Dual role for adenine nucleotides in the regulation of the atrial natriuretic peptide receptor, guanylyl cyclase-A

被引:54
作者
Foster, DC
Garbers, DL
机构
[1] Univ Texas, SW Med Ctr, Howard Hughes Med Inst, Dallas, TX 75235 USA
[2] Univ Texas, SW Med Ctr, Dept Pharmacol, Dallas, TX 75235 USA
关键词
D O I
10.1074/jbc.273.26.16311
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
The ability to both sensitize and desensitize a guanylyl cyclase receptor has not been previously accomplished in a broken cell or membrane preparation. The guanylyl cyclase-A (GC-A) receptor is known to require both atrial natriuretic peptide (ANP) and an adenine nucleotide for maximal cyclase activation. When membranes from NIH 3T3 cells stably overexpressing GC-A were incubated with ATP, AMPPNP, or ATP gamma S, only ATP gamma S dramatically potentiated ANP-dependent cyclase activity. When the membranes were incubated with ATP gamma S and then washed, GC-A now became sensitive to ANP/AMPPNP stimulation, suggestive that thiophosphorylation had sensitized GC-A to ligand and adenine nucleotide binding. Consistent with this hypothesis, the ATP gamma S effects were both time- and concentration-dependent. Protein phosphatase stability of thiophosphorylation (ATP gamma S) relative to phosphorylation (ATP) appeared to explain the differential effects of the two nucleotides since microcystin, beta-glycerol phosphate, or okadaic acid coincident with ATP or ATP gamma S effectively sensitized GC-A to ligand stimulation over prolonged periods of time in either case, GC-A was phosphorylated in the presence of [gamma(32)P]ATP, and the mag nitude of the phosphorylation was increased by the addition of microcystin. Thus, the phosphorylation of GC-A correlates with the acquisition of ligand sensitivity. The establishment of an in vitro system to sensitize GC-A demonstrates that adenine nucleotides have a daul function in the regulation of GC-A through both phosphorylation of and binding to regulatory sites.
引用
收藏
页码:16311 / 16318
页数:8
相关论文
共 33 条
[1]  
ANANDSRIVASTAVA MB, 1987, J BIOL CHEM, V262, P4931
[2]   CHARACTERIZATION OF ATP-STIMULATED GUANYLATE-CYCLASE ACTIVATION IN RAT LUNG MEMBRANES [J].
CHANG, CH ;
KOHSE, KP ;
CHANG, B ;
HIRATA, M ;
JIANG, B ;
DOUGLAS, JE ;
MURAD, F .
BIOCHIMICA ET BIOPHYSICA ACTA, 1990, 1052 (01) :159-165
[3]  
CHINKERS M, 1991, J BIOL CHEM, V266, P4088
[4]  
CHINKERS M, 1992, J BIOL CHEM, V267, P18589
[5]   THE PROTEIN-KINASE DOMAIN OF THE ANP RECEPTOR IS REQUIRED FOR SIGNALING [J].
CHINKERS, M ;
GARBERS, DL .
SCIENCE, 1989, 245 (4924) :1392-1394
[6]  
DOMINO SE, 1991, METHOD ENZYMOL, V195, P345
[7]   THE FAMILY OF GUANYLYL CYCLASE RECEPTORS AND THEIR LIGANDS [J].
DREWETT, JG ;
GARBERS, DL .
ENDOCRINE REVIEWS, 1994, 15 (02) :135-162
[8]   NUCLEOSIDE PHOSPHOROTHIOATES [J].
ECKSTEIN, F .
ANNUAL REVIEW OF BIOCHEMISTRY, 1985, 54 :367-402
[9]   A RECEPTOR GUANYLYL CYCLASE EXPRESSED SPECIFICALLY IN OLFACTORY SENSORY NEURONS [J].
FULLE, HJ ;
VASSAR, R ;
FOSTER, DC ;
YANG, RB ;
AXEL, R ;
GARBERS, DL .
PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES OF THE UNITED STATES OF AMERICA, 1995, 92 (08) :3571-3575
[10]  
GARBERS DL, 1994, J BIOL CHEM, V269, P30741